Download CHAPTER 25 - RNA Viruses of Medical Importance

BIOL 2320
J.L. Marshall, Ph.D.
CHAPTER 25 - RNA Viruses of Medical Importance*
*Lecture notes are to be used as a study guide only and do not represent the comprehensive information you will need to know for
the exams.
RNA viruses only have the nucleic acid RNA encased within their capsids. The RNA is sometimes segmented into multiple strands.
RNA that can be directly translated into protein is said to be “positive sense” (+ssRNA) and RNA that cannot be directly translated
into protein is “negative sense” (-ssRNA) – the latter must first be “reversed” prior to translation; the virus has enzymes to
accomplish this. RNA is highly mutable and the high mutation rate results in RNA viruses quickly adapting to many vaccines; in some
cases, vaccines seem nearly impossible (e.g. cold viruses). RNA viruses can be enveloped or nonenveloped (Table 25.1 and System
Profile 25.1).
25.1 Enveloped Segmented Single-Stranded RNA Viruses
The Biology of Orthomyxoviruses: Influenza
Orthomyxoviruses are influenza viruses A, B, and C. Type A causes the most cases of infection. Influenza or flu is characterized by
sudden onset of fever, chills, muscle ache (myalgia), and headache. Also observed are cold symptoms: nasal inflammation and
discharge, sore throat, and cough. It is transmitted person-to-person by the aerosols created by coughing and sneezing. Stomach flu
is a misnomer, but symptoms may occasionally include loss of appetite, diarrhea and emesis (vomiting). The virus attaches to and
multiplies in the cells of the respiratory tract.
Flu is caused by enveloped, cylindrical capsid, -ssRNA orthomyxoviruses (fig. 25.1, pg. 749). Influenza viruses are divided into 3 main
categories: A, B, and C (Table 25.1). A and B are responsible for seasonal epidemics. Type C causes mild respiratory illnesses with few
or no symptoms.
Influenza types A or B viruses cause epidemics of disease almost every winter. In the United States, these winter influenza epidemics
can cause illness in 10% to 20% of people and are associated with an average of 36,000 deaths and 114,000 hospitalizations per
year. Getting the flu vaccine can prevent illness from types A and B influenza. The flu vaccine does not protect against type C
influenza.
Influenza type A viruses are divided into subtypes based their receptor spike proteins. These proteins are called hemagglutinin (H)
and neuraminidase (N). Hemagglutinin is used to bind to respiratory cells. Neuraminidase is an enzyme that breaks down
respiratory mucus (fig. 25.2). The current subtypes of influenza A viruses found in people are: H1N1, H2N2, and H3N2. Influenza B
virus is not divided into subtypes. Influenza A(H1N1), A(H3N2), and influenza B strains are included in each year’s influenza vaccine.
Avian influenza A (“bird flu”) is characterized as H5N1.
Gradual evolution of the surface protein components is called antigenic drift (usually type B); this is caused by random mutations.
Abrupt changes in combinations of different hemagglutinin and neuramidase receptors is called antigenic shift (fig. 25.3): shift is
caused by the recombination of different strands of RNA from both an animal virus and a human virus during coinfection of one
host. Type A can undergo both drift and shift. Major antigenic changes in these viral coat receptors causes an outbreak of new
strains of flu. The results are an epidemic or pandemic. The young who are immunologically naive to viral exposure and the elderly
who have suppressed immune systems are the hardest hit. When a new strain appears, however, everyone is susceptible because
they have had no prior exposure and therefore have no antibodies against it.
Emerging Avian Influenza Viruses
Prior to the hysteria over the new swine flu, it was worried that an antigenic shift might take place between the A(H5N1) avian virus
(“bird flu”) and a strain of human flu virus, thus making a radically different strain (e.g. H5N2). The spring of 2009 has seen the
emergence of a “new” swine flu, although it was only a mutated H1N1. See the CDC for further comment on avian and swine flu.
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Epidemics and pandemics: A pandemic is a worldwide outbreak. 1918-19 was "Spanish flu": Type A (H1N1): 500,000-600,000 deaths
in the U.S. and 20-30 million worldwide. By today's population numbers, 600,000 deaths would equate to 1.4 million people. Public
gatherings were prohibited. October 1918 was the deadliest month in American history: 195,000 people died in 30 days. In an
average year 30,000 people die of influenza.
Epidemiology and Pathology of Influenza A
Influenza A is an acute, highly contagious respiratory illness affecting people of all ages. It does show a seasonal tendency. Its
outbreaks has been noted throughout history. The “flu” shows regularity in its outbreaks, so vaccines are prepared.
Mode of Influenza Transmission
It is transmitted by inhalation of virus-laden aerosols and droplets. Fomites can also be a source. It is most likely to get transmitted in
crowded areas and poor ventilation. Contact with swine, chicken and other poultry can also serve as a mode of transmission. It is
non fatal in most people, but children and the elderly can die from infection.
Infection and Disease
Influenza binds to the ciliated cells of the respiratory mucosa, which it then destroys that layer. The illness is characterized by fever,
headache, myalgia, shortness of breath, and coughing.
A weakened host defense system by the flu leaves some in the population susceptible to contracting pneumonia. Other
complications include bronchitis, meningitis, and in some cases death.
Diagnosis, Treatment, and Prevention of Influenza
Treatment only to relieve symptoms. Amantadine is a synthetic tricyclic amine that is used for prophylaxis during influenza A
epidemics (rimantadine is another choice of treatment). Oseltamavir (Tamiflu™) and zanamivir (Relenza™) are effective against the
H1N1 swine flu, but amantadine and rimantadine are not. Vaccines against influenza virus are available but must be renewed every
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year. Vaccinations are usually only recommended for young children, the elderly, and for individuals at high risk (health care
workers). Check CDC for updates.
Influenza Vaccination is recommended year as the antigens on the virus changes constantly. Anyone over the age of 6 months can
take the vaccine. There are several vaccines. A serious complication of the flu vaccine is Guillain-Barre’ syndrome, a neurological
disorder.
Aspirin is contraindicated while suffering from influenza. Ingestion of aspirin has been known to lead to a degenerative disease of
the CNS called Reye's syndrome. It has been implicated with influenza and parainfluenza virus strains. It is a complication of
influenza A, influenza B, and varicella (chickenpox) infections. The syndrome is characterized by a swelling of the brain and a fatty
degeneration of the liver. Most cases (15%) occur in children under 14. Symptoms: While recovering from flu and chickenpox, the
patient begins vomiting repeatedly. Lethargy, disorientation and irritability followed by unconsciousness and death. Some children
survive but with permanent brain damage.
See also Pathogen Profile #1 Influenza virus.
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See http://www.cdc.gov/flu/protect/whoshouldget.htm for current recommendations.
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25.2 Enveloped Nonsegmented Single-Stranded RNA Viruses
Paramyxoviruses
Important human paramyxoviruses are Paramyxovirus (para-influenza and mumps virus), and Morbillivirus (measles virus), all of
which are readily transmitted through respiratory droplets. The paramyxoviruses initiate cell to cell fusion, called a syncytium, or
multi-nucleate giant cells (fig. 25.4).
Mumps: Epidemic Parotitis
Mumps is characterized by fever, swelling of the salivary (parotid) glands (fig. 25.5). It is caused by a paramyxovirus called mumps
virus (fig. 25.5).
EPIDEMIOLOGY AND PATHOLOGY OF MUMPS Humans are the exclusive natural reservoir. It is transmitted through salivary and
respiratory secretions. Incubation is 2 – 3 weeks. It is characterized by swollen salivary (parotid) glands. Those infected can recover
with permanent immunity.
COMPLICATIONS IN MUMPS Mainly childhood disease (5-10 years of age) although adults can catch it. In adults, complications can
occur including: orchitis (inflammation of the testes), meningitis (inflammation of the lining of the brain, encephalitis (inflammation
of the brain), or pancreatitis (inflammation of the pancreas). Transmission is person-to-person by salivary or respiratory secretions.
Adults usually contract the disease from children.
Diagnosis, Treatment, and Prevention of Mumps
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An ELISA test can be used to diagnose the presence of the virus. Vaccination of children (MMR vaccine ) reduces the source of
infection and the number of susceptible individuals. Adults may be treated with hyperimmune serum IgG to prevent orchitis and
prevent possible male sterility.
Note: Despite much speculation, there is no link between the MMR vaccine and autism.
Measles: Morbillivirus Infection
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Measles (rubeola ) or red measles is caused by Morbillivirus, an enveloped, cylindrical capsid, -ssRNA paramyxovirus. Measles
infects the respiratory tract, specifically the epithelium, and the lymph nodes that drain the respiratory tract. Initial symptoms are
like the common cold: sore throat, low-grade fever, and cough. Allergic reaction (e.g., nasal congestion) and conjunctivitis may also
occur.
Epidemiology of Measles
A very contagious infectious disease transmitted by aerosols. Humans are the reservoir. It is spread by crowding conditions,
malnutrition and inadequate health care. It is very important to have children vaccinated.
Infection, Disease, and Complications of Measles
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For young children this may now be the MMRV vaccine which includes varicella (against chickenpox).
http://www.cdc.gov/vaccinesafety/vsd/mmrv.htm
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Note: German measles, a.k.a. rubella, is an unrelated viral disease (see below).
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As the disease spreads, Koplik spots (red dots with blue centers) appear on the lateral oral mucosa (inside roof of the mouth). A rash
appears on the neck and face and spreads over the body (fig. 25.6). Incubation period 10-21 days. Acute stage with rash (4-5 days).
Transmission is person-to-person by aerosols and respiratory secretions. It occurs in epidemic proportions every 5-7 years. Measles
can lead to encephalitis, subacute sclerosing panencephalitis, blindness, and deafness.
Diagnosis, Treatment, and Prevention of Measles
Age, exposure and time of year are all used to help diagnose measles. Treatment relies on reducing the fever, suppressing cough and
replacing fluids. Vaccination by a attenuated vaccine is done. Passive immunity can be transferred from mother to child and protect
children under 5 or 6 months of age. Vaccine (MMR) available.
See Table 25.3 for a comparison of the two forms of measles. See also Pathogen Profile #2Morbillivirus (measles virus)
Rhabdoviruses
Hydrophobia or rabies is a disease of the CNS transmitted via zoonosis. The initial infection generally begins at the site of an animal
bite and spreads to the nervous system. It results in deterioration of the brain and death. Rhabdovirus is the etiologic agent (fig.
25.7). It is an enveloped, bullet-shaped, cylindrical capsid, -ssRNA genome virus. The virus replicates in the brain, spinal cord, and
salivary glands. The virus can be found worldwide in domestic as well as wild animals (especially rats, bats, coyotes, and raccoons)
(fig. 25.8). Transmission to humans is generally through bites, although you should never handle dead animals (esp. bats) since you
can still become infected if accidentally cut by their teeth.
Epidemiology of Rabies
Rabies is a slow, progressive zoonotic disease. It can cause fatal meningoencepalitis. The primary reservoirs are wild mammals such
as canines, skunks, raccoons, cats and bats. It can spread to domestic cats and dogs.
Infection and Disease
The virus usually enters by a rabid animal bite. Inside the body, the virus replicates at the infection site, especially in the peripheral
nerve cells. Nothing produced by the immune system inhibits growth of the virus (i.e., interferon).
Clinical Phases of Rabies
The amount of time it takes for the organism to reach the brain depends upon the bite location (hand: 6-12 weeks to reach the
brain; head: 2-3 weeks). In humans, death usually occurs 2-3 weeks after the onset symptoms, and there are no symptoms until the
virus begins to multiply within the brain and spinal cord.
Symptoms: malaise, fever, weakness, hydrophobia (fear of water), paralysis, acute renal failure, coma and death. The clinical phases
are: prodromal – fever, vomiting, headache; furious – acute neurological involvement, seizures; dumb – paralysis.
Diagnosis and Management of Rabies
Prevention: Reduction of the disease through vaccination of domestic animals and vaccination of humans in high risk jobs,
controlling stray and wild animals.
Active immunization = 6 inoculations of chemically inactivated virus (human diploid cell vaccine): 5 intramuscular injections over 30day period and 1 injection two months later.
Treatment:
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The bad news: There is no treatment after the symptoms appear. 100% fatal after the symptoms appear.
The good news: If treated BEFORE symptoms appear, nearly 100% curable. Rabies is the only disease where immunization can be
started after exposure to prevent the disease because antibody production develops faster than the time it takes the virus to travel
to the brain or spinal cord. Once the symptoms begin, there is little or nothing that can be done. After exposure, persons are
passively immunized with human rabies immune globulin or with horse anti-rabies serum and actively immunized with human
diploid cell vaccine. The vaccination is given prophylactically to those who work with animals. Three doses are given at day 1, day 7,
and day 21 followed by a booster every year or every other year.
25.3 Other Enveloped RNA Viruses: Coronaviruses, Togaviruses, and Flaviviruses
Coronaviruses
Coronaviruses are large RNA spiked enveloped viruses. Common in domesticated animals, and are responsible for the spread in
other pigs, dogs, cats and poultry.
Severe Acute Respiratory Syndrome-Associated Coronavirus
SARS was reported in 2002 as an acute respiratory illness. Originated in Asia. Spread to other countries by those who were in Asia at
the time of the outbreak. Symptoms include a fever and overall body aches.
Diagnosis relies on the exclusion of other diseases. PCR is used to confirm the diagnosis.
Coronaviridae
Coronaviruses are large RNA viruses with distinctive spikes on their envelopes (for which they are named). Common in domesticated
animals and responsible for epidemic respiratory, enteric, and neurological diseases in pigs, dogs, cats, and poultry. Three types of
human coronavirus have been characterized. One of these is an etiologic agent of the common cold (see notes on Rhinoviruses
below).
Another, which appeared in 2002, is the SARS virus. Initial results of genomic sequencing indicate that the SARS virus is distinct from
all previously recognized coronaviruses.
SARS, or severe acute respiratory syndrome begins with a fever greater than 100.4°F [>38.0°C]. Other symptoms may include
headache, an overall feeling of discomfort, and body aches. Some people also experience mild respiratory symptoms. After 2 to 7
days, SARS patients may develop a dry, nonproductive cough that might be accompanied by or progress to the point where
insufficient oxygen is getting to the blood. In 10% to 20% of cases, patients will require mechanical ventilation.
The disease was first reported among people in Guangdong Province (China), Hanoi (Vietnam), and Hong Kong. It has since spread
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rapidly to other countries via air travelers. SARS has been added to the list of quarantinable communicable diseases.
Treatment:
CDC currently recommends that patients with SARS receive the same treatment that would be used for any patient with serious
community-acquired atypical pneumonia of unknown cause. Several treatment regimens have been used for patients with SARS, but
there is insufficient information at this time to determine if they have had a beneficial effect. Therapy has included antiviral agents
such as oseltamivir or ribavirin. Steroids also have been administered orally or intravenously to patients in combination with
ribavirin and other antimicrobials.
For the latest information on SARS, see the CDC website: http://www.cdc.gov/niosh/topics/SARS/.
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There have been 10 cases now where treatment was successful after symptoms appeared. However, this treatment is still
experimental, and only rarely successful.
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http://www.cdc.gov/ncidod/sars/executiveorder040403.htm
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Rubivirus: The Agent of Rubella
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German measles, a.k.a. Rubella is caused by the Rubivirus, an enveloped, icosahedral, +ssRNA virus. The disease is characterized by
macular rash and accompanied by a low-grade fever. Infects respiratory tract and spreads to other organs. Early symptoms include
fever, nasal discharge, and enlarged lymph nodes. The rash is an allergic response (i.e., hypersensitivity) to the viral antigens.
Epidemiology of Rubella
It is endemic world wide. Infection is done through contact with respiratory secretions. It moderately communicable, thus close
living conditions are necessary to spread the virus. Transmission is by aerosols, direct person-to-person contract and nasal
secretions. Vaccine available (MMR). Congenital rubella is possible.
Infection and Disease
If contracted during the first trimester of pregnancy, it can result in spontaneous abortion or developmental abnormalities, including
brain damage, mental retardation, deafness, congenital cataracts, blindness, heart defects, bone lesions, enlarged spleen, enlarged
liver, and low birth weight. Fig. 25.9.
POSTNATAL RUBELLA Pink rash appears (fig. 25.9). In adults it can cause joint pain. This form is generally mild and produces lasting
immunity.
CONGENTIAL RUBELLA Rubella is teratogenic, it can be transmitted to the fetus. Infection of the first trimester can induce a
miscarriage. If the infant is born with rubella it can lead to physical and mental abnormalities.
Diagnosis and Prevention
It is confirmed with serological tests and virus isolation. IgM tests can determine the infection. Control of rubella is done by vaccine –
MMR.
Rubivirus
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German measles, a.k.a. Rubella is caused by the Rubivirus, an enveloped, icosahedral, +ssRNA virus. The disease is characterized by
macular rash and accompanied by a low-grade fever. Infects respiratory tract and spreads to other organs. Early symptoms include
fever, nasal discharge, and enlarged lymph nodes. The rash is an allergic response (i.e., hypersensitivity) to the viral antigens.
If contracted during the first trimester of pregnancy, it can result in spontaneous abortion or developmental abnormalities, including
brain damage, mental retardation, deafness, congenital cataracts, blindness, heart defects, bone lesions, enlarged spleen, enlarged
liver, and low birth weight. Fig. 25.9, pg. 760.
Transmission is by aerosols, direct person-to-person contract and nasal secretions.
Vaccine available (MMR).
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Not to be confused with rubeola, caused by Morbillivirus.
Not to be confused with rubeola, caused by Morbillivirus.
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Hepatitis C Virus
Hepatitis C is an RNA virus. It is known as the “silent epidemic” because people may have it and not know it. It can cause liver
failure.
Transmission and Epidemiology
Transmitted similarly as hepatitis B (HBV) – through blood contact such as needles and transfusions.
Pathogenesis and Virulence
HCV can establish chronic infections. It seems to be able to evade the immune system. Screening for HCV was done when screening
was done for HIV, therefore a large percent of the population have HCV.
Signs and Symptoms
Has similarities to HBV. People who have it develop chronic liver disease without overt symptoms. Can give rise to liver cancer.
Diagnosed with detection of antibodies.
Prevention and Treatment
There is currently no vaccine due to its wide antigenic variation. New treatment is done such as interferon and drugs such as
ribavirin and sofosbuvir to lessen the damage to the liver.
3. Filoviridae – FYI!!!
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Hemorrhagic viruses : Ebola virus and Marburg virus. Cases of Ebola hemorrhagic fever were detected in 1976. There were 318
cases with 280 fatalities in Zaire, and 284 cases with 141 fatalities in Sudan. In 1995, 316 cases with 245 fatalities occurred in Zaire.
Ebola belongs to the virus family Filoviridae. Genetic and antigenic analyses have identified at least four subtypes: subtype Zaire
(1976 & 1995), subtype Sudan (1976 & 1979), subtype “Reston” isolated from research monkeys in Reston, Virginia in 1989 (the
monkeys were from the Philippines), and subtype Côte d’Ivoire (1994).
Since there is no effective treatment and due to its inherent virulence, Ebola is the most deadly virus known, with nearly a 90%
mortality rate. Incubation is 2 to 21 days.
Symptoms: include sudden onset of fever, weakness, muscle pain, headache and sore throat, followed by diarrhea, rash, limited
kidney and liver functions, both internal and external bleeding. Diagnosis requires specialized serological tests from blood specimens
(not commercially available) or isolating the virus. These tests present an extreme biohazard (Biosafety Level P4).
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For a fascinating account of Ebola and the Reston Virginia outbreak, read: The Hot Zone by Richard Preston.
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Treatment: No specific treatment. No vaccine. Severe cases require intensive supportive care. There is no long protection against the
disease.
Prevalence: Zaire, Sudan, Côte d’Ivoire, and Gabon. The natural reservoir is unknown. Ebola-related filoviruses have been isolated
from cynomolgus monkeys (Macacca fascicularis) imported to the U.S. from the Philippines.
Transmission: Direct contact with blood, secretions, organs, or semen. Transmission through semen may occur up to 7 weeks after
clinical recovery. Transmission can occur from handling ill and dead infected patients. The 1976 Zaire outbreak occurred via
contaminated syringes and needles.
Containment:
1. isolation of patient
2. practice strict barrier nursing techniques
3. immediate burial or cremation of the dead
Contacts: Any person having close contact with patients should be kept under surveillance for 3 weeks, including body temperature
checks twice a day, immediate hospitalization and isolation if temperature exceeds 38.3°C (101°F).
2. Flaviviridae – FYI!!!
West Nile Virus is a flavivirus commonly found in Africa, West Asia, and the Middle East. It is closely related to St. Louis encephalitis
virus also found in the United States. The virus can infect humans, birds, mosquitoes, horses and some other mammals. Can be
transmitted as a zoonosis from mosquitoes to humans.
West Nile fever is a case of mild disease in people, characterized by flu-like symptoms. West Nile fever typically lasts only a few days
and does not appear to cause any long-term health effects. See http://www.dshs.state.tx.us/idcu/disease/arboviral/westNile/ for
statistics on West Nile cases in Texas. In the US there were 627 reported cases.
More severe disease due to a person being infected with this virus can be West Nile encephalitis, West Nile meningitis, or West Nile
meningoencephalitis. Encephalitis refers to an inflammation of the brain, meningitis is an inflammation of the membrane around the
brain and the spinal cord, and meningoencephalitis refers to inflammation of the brain and the membrane surrounding it. Very rare
cases are fatal (2 deaths in Texas in 2011), although the news media have tended (typically) to exaggerate the danger.
See CDC for U.S. statistics (http://www.cdc.gov/ncidod/dvbid/westnile/index.htm)
25.5 Retroviruses and Human Diseases
HIV Infection and AIDS
AIDS or Acquired Immune Deficiency Syndrome is caused by a retrovirus, the human immunodeficiency virus (HIV) (fig. 25.11) with
continuing devastating effects worldwide. The virus infects and destroys helper T-lymphocytes (TH CD4+) and macrophages, and thus
destroys the host's ability to combat a huge range of opportunistic infections and cancers. Like some other viruses, HIV can cross the
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placenta ; babies can be born with AIDS. Given the chronic nature of AIDS, a spectrum of disease is associated with HIV infections.
Characteristics of Human Retroviruses
HIV is a retrovirus. Most retroviruses can cause cancer and death. They are names retroviruses because of an enzyme they carry
called reverse transcriptase (RT) which converts its RNA to DNA. The retroviral DNA is then incorporated into the host’s genome.
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However, current treatments have reduced the transmission rate during pregnancy to 5% to 11%
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The most common human retroviruses are HIV and T-cell lymphotropic viruses I and II (HTLV-I and HTLV-II). HIV is an enveloped RNA
virus (fig. 25.11a). HIV infects cells with a CD4 marker plus a co-receptor (fig. 25.11b). Initially, symptoms include fever,
lymphadenopathy, fatigue, diarrhea, weight loss, neurological syndromes, and opportunistic infections. Not everyone who becomes
infected or is antibody-positive develops AIDS. Also, a small population exists that has a mutation which prevents them from
developing AIDS altogether even after repeated exposure to the virus.
It is usually with the first appearance of AIDS-defining illnesses that the most severe and life-threatening phase of AIDS begins.
Patients may have antibodies against HIV and one or more of several chronic infections (e.g., hepatitis, amebiasis, or fungal
infections).
Examples:
1. suffering from characteristic opportunistic infections (e.g., pneumonias caused by a fungus, Pneumocystis jiroveci; fungal
meningitis caused by Cryptococcus neoformans; Candida albicans that attack the oral, pharyngeal and esophageal mucosa (i.e.
oral thrush); tuberculosis; protozoans likeToxoplasma gondii which causes toxoplasmosis of the brain and Cryptosporidium
which causes diarrhea.
2. afflicted by characteristic cancers—such as, Kaposi's sarcoma, which causes nodular purple lesions on the skin. Other effects
include lymphadenopathy, weight loss, hemorrhage, perforation and intestinal obstruction. Additional cancers common to AIDS
patients are epithelial carcinomas of the skin, mouth, and rectum, and lymphomas.
Epidemiology of HIV Infection
One theory on HIV origin is SIV. There was a chimpanzee to human transfer.
Modes of Transmission
Occurs mainly through sexual intercourse and transfer of blood or blood products. Babies can be infected before or during birth, as
well as through breast milk.
Transmission (fig. 25.12):
1. sexually transmitted by vaginal or anal sex
2. sharing needles among intravenous drug users
3. transfusion of blood or blood products
4. congenital (from HIV crossing the placenta) and neonatal AIDS (from breast feeding)
5. risks involving medical and dental personnel (accidental needle sticks)
The risk of transmission through casual contact with saliva, tears, urine and fecal matter is too small to be measured, making
quarantine of infected individuals unnecessary. It cannot be transmitted by mosquitoes, in swimming pools, through food or
fomites. Common sense and education are the best weapons against the disease at this stage.
Vaccine development is underway. Constructing a vaccine against HIV is particularly difficult due to the high degree of mutability in
the viral genome and the fact that the virus hides inside infected T cells.
AIDS Morbidity
AIDS is a notifiable disease. It has epidemic / pandemic patterns. Sexual intercourse is the most common form of transmission. It is
in all ethnic populations (fig. 25.13) and across every state in the US.
Very few people in the population have a natural resistance to HIV. They are missing an important co-receptor, CCR5, that is needed
for HIV to infect.
Treatment of HIV infected mothers with AZT has reduced the mother to fetus transmission.
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Pathogenesis and Virulence Factors of HIV
The clinical spectrum of an HIV infection is from acute early symptoms to end stage AIDS. The pathology of HIV hinges on the viral
load and the level of T cells in the blood. Initial symptoms are acute and show “mono” like symptoms. The levels of the virus and
antibodies to HIV changes over the course of the infection (fig. 25.15 and fig. 25.16). Once the CD4 cell levels drop below 200
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cells/mm , then the person will have AIDS-defining illnesses. Some of the most severe complications are neurological.
Viral multiplication cycle:
HIV causes damage to the immune system by infecting and reproducing within helper T-lymphocytes (fig. 25.14). As the virus fuses
with the host cell, the outer envelope is lost and the naked capsule is freed into the cytoplasm. The RNA is released into the
cytoplasm and then undergoes transformation into DNA. Like all retroviruses, HIV carries its own reverse transcriptase enzyme. This
enzyme first turns the viral RNA into ssDNA. The ssDNA is “filled out” into dsDNA which can then integrate into the host cell’s DNA in
a lysogenic state and remain quiescent for 10-15 years. Transcription of the viral DNA is activated by unknown signals (probably
cellular stress) which then lead to the mRNAs being translated into the proteins necessary for new capsids. Maturation and release
of virions then proceeds.
Without T-helper cells, the immune response to infectious agents is effectively shut down. HIV can also invade macrophages.
Infected macrophages in the brain cause deterioration of the CNS, leading to memory loss, mental retardation, paralysis and death.
Memory loss and emotional changes are among the first symptoms of the disease.
Diagnosis of HIV Infection
A person must test HIV positive for the virus. Most lab tests are based on antibodies to the virus. ELISA is often used as the first
screening for HIV, but the ELISA assay can give false positives. Use of a Western blot is done to confirm the presence of HIV.
Persons are described as having AIDS when they test positive for the virus and they have a low CD4 T-cell count and they have an
AIDS defining illness. See Making Connections AIDS-Defining Illnesses (ADIs).
Preventing HIV Infection
Avoid sexual contact with someone who is HIV positive. Use protection such as a condom.
HIV becomes latent in cells. Its surface antigens constantly mutate, so a reliable vaccine has yet to be developed.
Treating HIV Infection and AIDS
Treatment (fig 25.17): There is no cure; however, current treatments are much more effective than they were twenty years ago.
Treatment includes supportive care and drugs to control opportunistic and HIV infections. The synthetic nucleoside analog AZT
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(azidothymidine) is a reverse transcriptase inhibitor that inhibits the replication of AIDS virus throughout the body; others in this
drug group include Didanosine (ddI), Epivir (3TC), and Stavudine (d4T). These lead to an improved immune function, weight gain,
increase of helper T-lymphocytes, reversal of mental retardation, cancer regression, decrease of infections and death rate. Protease
inhibitors (e.g., Crixivan™, Norvir™, and Agenerase™) block the action of an HIV enzyme involved in the final assembly and
maturation of the virus. Side effect is anemia because the drug affects the synthesis and development of red blood cells.
Combination therapy called HAART (for highly active antiretroviral therapy) using two reverse transcriptase inhibitors and a
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protease inhibitor in a single pill; this is supplemented with a receptor blocker and an integrase inhibitor .
For more information see the CDC: http://www.cdc.gov/hiv See also Pathogen Profile #3Human immunodeficiency virus 1 and 2
(HIV-1, HIV-2)
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Nevirapine™ and efavirenz (Sustiva™) are reverse transcriptase inhibitors that act by altering its structure.
Integrase is the enzyme HIV uses to become a provirus (see Ch. 6 notes).
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Human T-Cell Lymphotropic Viruses
Leukemia is the name of a disease that is a malignant form of white blood cells. Leukemias has acquired rather than inherited.
Leukemias tend to be viral based. The human T-cell lymphotropic virus I (HTLV-I) is associated with a form of adult T-cell leukemia.
There are a variety of symptoms that are associated with T-cell leukemias. These leukemias are caused by a retrovirus that can
induce cancer. Intimate / close contact is needed to transmit the virus. It is thought that the virus is passed through blood / blood
products.
25.6 Nonenveloped Single-Stranded and Double-Stranded RNA Viruses
Picornaviruses and Caliciviruses
Small RNA viruses (fig. 25.18a). Representatives of the picornaviruses are listed in Table 25.4.
Poliovirus and Poliomyelitis
Poliomyelitis or polio is a disease of the CNS, characterized by destruction of nerve tissue in brain and spinal cord and muscle
paralysis. The causative agent is a naked, icosahedral capsid, + ssRNA picornavirus (fig 25.18b). Destruction of nerve tissue (fig.
25.19) can lead to paralysis and death. From paralysis, inability to stimulate affected muscles can lead to wasting away (atrophy).
Humans appear to be the only host species. It is an ancient disease.
Epidemiology of Polio
Transmission is person-to-person, via contaminated food and water (e.g., saliva, feces) (fig. 25.19). The symptoms can be mild to
severe. Mild symptoms include sore throat, headache, fever, nausea (all caused by multiplication of the virus in the throat and
intestines).
From the throat, tonsils, or intestines, the virus can spread to the circulatory system. If the virus enters the nervous system, it causes
damage that can lead to paralysis. Polio virus is neurotropic, meaning it infiltrates the motor neurons of the spinal cord.
Paralytic Disease
It invades the motor neurons causing various degrees of flaccid paralysis. Bulbar poliomyelitis causes damage of the respiratory
organs requiring the patient to have breathing treatments in an “iron lung” (fig. 25.21a). Common sites of muscular deformities are
arms and legs (fig. 25.21b).
Diagnosis, Treatment and Prevention of Polio
In 1955 Dr. Jonas Salk developed the vaccine which has since come to bear his name. The Salk vaccine (IPV) is a formalin-inactivated
virus used in injections over several months with boosters every five years. Albert Sabin later introduced an oral polio vaccine (OPV),
but recently physicians have returned to the Salk vaccine. There is currently a world-wide effort to eliminate polio as was
accomplished for small pox.
Treatment: no effective treatment other that palliative.
See also Pathogen Profile #4 Poliovirus
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Human Rhinovirus (HRV)
The common cold is caused by the rhinoviruses, is characterized by "stuffy nose, scratchy throat," general malaise, headache, sore
throat, sneezing and watery nasal discharge (discharge can thicken and turn yellowish). Typically afebrile (fever free). Incubation
period is 1-4 days, runs its course in 4-7 days. Complications include sinusitis and otitis. Those colds occurring in fall and spring are
usually caused by rhinovirus (one of the picornaviruses; responsible for approximately 50% of cold cases). Rhinovirus is a naked,
icosahedral capsid, +ssRNA.
NOTE: Other “cold” causing viruses: paramyxoviruses, enteroviruses, coronaviruses, and adenoviruses. Some 200 different viruses
and/or strains can cause cold-like symptoms, so vaccine development is virtually impossible.
Epidemiology and Infection of Rhinoviruses
The mode of transmission is person-to-person or person-to-fomite-to-person with mucous membranes of the nose and eyes being
the portal of entry. The infection can occurs during all times of the year.
Control of Rhinoviruses
Treatment: PREVENTION is the best medicine: the most significant single factor in the spread of colds is contamination of hands
with mucous secretions – so wash those hands! Recommendations: fluids and get bed rest. Over-the-counter medications do
nothing to lessen the duration of symptoms; they only relieve some of those symptoms (i.e. palliative care).
See the CDC for helpful information on the common cold and relieving symptoms: http://www.cdc.gov/getsmart/antibioticuse/URI/colds.html
Miscellaneous Viruses and Pathologies – FYI!!!!!
1. Viral pneumonia
In children:
Respiratory Syncytial Virus (RSV) causes severe respiratory infections (leading to pneumonia) among infants and children less than
1 year of age. Approximately 100,000 children are hospitalized in the US each year.
Treatment: For children with mild disease, no specific treatment is necessary other than the treatment of symptoms (e.g.,
acetaminophen to reduce fever). Children with severe disease may require oxygen therapy and sometimes mechanical ventilation.
Ribavirin aerosol may be used in the treatment of some patients with severe disease. Some investigators have used a combination
of immune globulin intravenous (IGIV) with high titers of neutralizing RSV antibody (RSV-IGIV) and ribavirin to treat patients with
compromised immune systems (these are very expensive: ~$1000/treatment).
In adults with chronic heart and lung disease or as a complication from other infections (flu, chickenpox), viral pneumonia may
develop. It is caused by influenza viruses, adenoviruses and respiratory syncytial viruses (RSV). Following flu-like symptoms, the
patient develops fever (about 102F), breathing difficulty, a cough and frothy blood-tinged sputum. Diagnosis is made by process of
elimination (i.e. "If it's not bacterial or fungal, it must be viral.")
CDC site: http://www.cdc.gov/rsv/index.html
Caliciviruses and Reoviruses
Characterized by nausea, vomiting, diarrhea, fever, cramps, headache and prostration. This is probably the nearest thing to what
most people describe as “stomach flu” (of which there is no such thing). It is extremely difficult to isolate and identify the causative
agent (done usually by process of elimination since the symptoms are nearly identical to those caused by bacterial toxin ingestion or
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infection). Rotavirus and Norwalk virus (norovirus) are known causes (fig. 25.24). Norwalk virus is now believed to cause 90% of all
cases of viral gastroenteritis. Norwalk has been implicated in a rash of infections on cruise ships. Rotavirus is most dangerous to
children, accounting for approximately 50% of cases, and greater than 600,000 deaths (globally) each year. The most significant
cause: fecal contamination in drinking water.
Transmission is the fecal-oral route via food, water or contaminated cooking utensils.
Treatment: prevention (wash hands); administration of fluids and electrolytes to prevent dehydration.
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25.7 Prions and Spongioform Encephalopathies
(also see section 6.8)
Prions were so named since they are proteinaceous infectious particles. That is, they are protein only. NO nucleic acid. See table
25.5 for properties of prions.
Prions are NOT viruses
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They are the agents responsible for transmissible spongiform encephalopathies (TSEs) such as Creutzfeldt-Jakob disease (CJD) . In
livestock, prions cause mad cow disease (fig. 6.21).
Pathogenesis and Effects of CJD
These diseases are transmissible, 100% fatal, chronic infections of the nervous system marked by the formation of vacuoles in nerve
cells and a spongy appearance of the cerebrum (fig. 25.25).
CJD – Symptoms include altered behavior, dementia, memory loss, impaired senses, delirium, and premature senility.
Uncontrollable muscle contractions continue until death, which usually occurs within one year of diagnosis.
Transmission and Epidemiology
Usually acquired through eating undercooked or raw organ meat, especially brain tissue. (Note: although I have never heard of the
prions being transmitted through rare beef – muscle tissue – that doesn’t mean it can’t happen; estimated rate of infection = 1 case
per 10 billion meat servings.)
Culture and Diagnosis
Done from a biopsied brain or nervous tissue. Usually, this is done post-mortem.
Prevention and/or Treatment
Treatment: None, 100% fatal.
Prevention: monitoring of livestock and discouraging the eating of rare or raw organ meat.
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Other names for spongiform encephalopathies in humans include Gerstmann-Strussler-Scheinker disease and kuru. Kuru refers
specifically to endemic encephalopathy once prevalent among tribes in New Guinea who practiced cannibalism. Prions were acquired
by ingesting infected brain tissue.
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