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VIROLOGY
• Small obligate intracellular parasites Viruses vary widely
in size and structure.
• All viruses enter living cells, and once inside, use
the cell to make more copies of the virus.
• VIRION: Complete virus particle : nucleic acid + protein
coat, which may be surrounded by an envelope
• It is the form in which the virus moves between cells or
hosts
• Bacteriophage are viruses that infect bacteria.
• Nucleic acid
• Capsid
• Viral envelope
Classification Of Viruses
According to
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1- Genome: DNA or RNA _-this could be either SS or DS
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2- Capsid: made of
A capsomeres 3 types of capsid symmetry
symmetry:
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Cubic (icosahedral)
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Helical
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Complex
3-Envelope: made of lipids
proteins and carbohydrates.
Viruses could be enveloped
or non-enveloped.
4- Host range: Infect specific
types of cells in specific host.
animal, plant, bacterial.
Bacterial viruses are called
bacteriophage
Viral Replication
- When a virus infects a cell, nucleic acid must be uncoated and gain
access to metabolic machinery of cell.
- Steps of Viral replication cycle:
• attachment
• penetration, with entry of .nucleic acid into cell
• early expression of virus genes (either directly by translation, if
virus contains "+" RNA, or indirectly after transcription and then
translation)
• replication of virus nucleic acid
• synthesis of new virion components
• packaging and assembly of new virions
• exit from cell
Transmission Of Viral Infection
• Enveloped Viruses: sensitive to harsh
environments. They tend to be transmitted
by respiratory, Parenteral or sexual route.
• Non-enveloped viruses are more stable
and often transmitted by fecal oral
transmission.
Viral Infection
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Once the virus is inside the host cell, two
different processes may occur.
1- Lytic Infection
Lytic Infections are caused when the virus
invades a host cell, makes copies of itself, and
eventually causes the cell to burst.
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2- Lysogenic Infections
occur when a virus finds a receptor site on a host cell and
injects its genetic material into the host.
- Rather than immediately manufacturing the new viral DNA, the host cell incorporates the viral
DNA(prophage) into its own DNA.
- When the host cell replicates or divides, the extra DNA acts just like an inert segment of DNA.
• It causes no harm to the host
• However, externaLstimuli can trigger the "extra DNA" to become virulent.
Antiviral Chemotherapy
Targets in the life cycle of viruses
Attachment
1- Using agents which mimic the virus-associated protein (VAP) and
bind to the cellular receptors. This may include VAP anti-idiotypic
antibodies, natural ligands of the receptor and anti-receptor
antibodies.
2-Using agents which mimic the cellular receptor and bind to the VAP.
This includes anti-VAP antibodies, recepor anti-idiotypic antibodies
extraneous receptor and synthetic receptor mimics.
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• A. Attachment of virus to receptor on host cell membrane.
• B. Antibody prevents adsorption of virus
Antiviral Chemotherapy
Uncoating
• Amantadine and rimantadine , have been
introduced to combat influenza. These
agents act on penetration /uncoating.
• PleconariI works against rhinoviruses,
which cause the common cold, by
bocking a pocket on the surface of the
virus that controls the uncoating process.
• Virus replication and synthesis Nucleic acid
replication
1-Nucleotide or nucleoside analogues that look like
the building blocks of RNA or DNA, but
deactivate the enzymes that synthesize the RNA
or DNA once the analogue is incorporated.
E.g. acyclovir against herpesyirus infections,
e.g. zidovudine (AZT) against HIV.
2-Integrase
Inhibit integrase enzyme that splices the
synthesized DNA into the host cell genome.
Viral synthesis:1- inhibition of transcription
2- Translation inhibition by antisense.
3- Assembley inhibition by protease inhibitors
Release
Two drugs named zanamivir (Relenza) and oseltamivir
(Tamiflu) that have been recently introduced to treat
influenza prevent the
Release of viral particle moleculenamed neuramindase
that is found on the surface of flu viruses, and also
seems to be constant across a wide range of flu strains.
• Immune system stimulation
1 - Interferons
• Inhibit viral synthesis in infected cells. One form
of human interferon named "interferon alpha" is
well-established as part of the standard
treatment for hepatitis B and C.
• 2-Monoclonal antibodies used against
Respiratory Syncytial Virus in children.
Viroids
Plant pathogen : consist of single-stranded RNA without the protein
coat that is typical for viruses.
Prions
- Infectious particles that are entirely protein.
- No nucleic acid
-Highly heat resistance
-Animal disease that affects nervous tissue
-Affects nervous tissue and results in
Bovine spongifonn encepahltits (BSE) "mad cow disease",
scrapie in sheep
kuru & Creutzfeld-Jakob Disease (CJD) in humans «•
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Medically Important Viruses
Herpes Simplex virus infections
Hepatitis
Childhood viral diseases
Heamoragic viral infections
Food born viral infections
Influenza
AIDs
Herpes Simplex Viruse
• Enveloped large double-stranded, DNA encased within
an icosahedral capsid virus. '
• Two strains HSV-1, HSV-2.
Infection
HSV-l causes cold sores or fever bilsters
whereas HSV2 is more often associated with genital herpes
• An infection by a herpes simplex virus is marked by watery blisters
in the skin or mucous membranes of the mouth, lips or genitals.
Lesions heal with a scab.
• After the initial, or primary, infection, HSV becomes latent in the cell
bodies of nerves in the area. Some infected people experience
sporadic , episodes of viral reactivation, followed by transportation
of the virus via the nerve's axon to the skin, where virus replication
and shedding occurs.
Transmission
• Horizontal transmission iLclose contact with an infected person who is
• shedding virus from the skin, in saliva or in secretions from the
genitals.
• Vertical transmission of HSV may occur between mother and child during
childbirth causing encephalitis, which can be fatal to the infant, but the risk
of infection is reduced if there are no symptoms or exposed busters during
delivery.
Treatment
• The antiviral most commonly used is Acyclovir or Valacyclovir.
• Diet: Research has also shown that the virus's growth is to a moderate
degree proportional to the ratio of the aminp acid arginine to the amino acid
lysine in the diet of infected individuals. A diet that is high in lysine and
low in arginine is recommended for people suffering from regular
outbreaks of HSV infections, because lysine interferes with arginine
metabolism that is required for HSV- replication.
Child hood Viral Diseases
Chikenpox
• Chickenpox (varicella) is an infectious disease
caused by the varicella-zoster virus
• Transmission: both direct skin-to-skin contact
and via respiratory droplets (coughing,
sneezing) from the infected individual.
• IP is 14-16 days, and the first sign of disease is
a asp? People are considered contagious for 2-5
days Before the onset of skin lesions and for 6
days after the last series of rashes have
appeared.
Complications:
• The most common complication is infection the lesion
with bacteria.
• Rare complication include" pneumonia or encephalitis.
Children who have weak immune systems, eczema, or
recent sunburns have more severe symptoms.
• Reactivation: Because the virus remains resting (latent)
in the parts of nerves that are near the spinal cord (nerve
roots) for life, about 1 in 10 adulte will get shingles
(zoster) when the virus reappears, usually under
conditions of stress to the body.
Hepatitis Viruses
VIRUS
Structure
Transmission
Hepatitis A virus
PICORNA, SS , non
enveloped,RNA
Oral-fecal
Hepatitis B virus
DNA virus
Parental ,Sexual
Vertical
Hepatitis C virus
RNA virus
Parental
Hepatitis D virus
RNA virus, SS
Parental
Code for one protein (delta
Vertical
antigen nucleocapside is
enclosed within an envelope
that carry HBs Ag
Hepatitis E virus
RNA , SS, non enveloped
Oral –fecal water born
Hepatitis G virus
RNA co-infection with
Hepatitis C
Parental
Vertical
Viral Hepatitis
Hepatitis B
• Structure
• Hepatitis B virus (HBV) is a member of the
Hepadnavirus family. It is an enveloped DS DNA
with an icosahedral nucleocapsid core. The
outer envelope carries the highly immunogenic
surface antigen (HBsAg) which is involved in
viral binding of, and entry into, susceptible cells.
• The virus is present in all body fluids
Hepatitis B Pathogenesis
Infections
1- Acute infection with hepatitis B virus is associated with acute viral
hepatitis - an illness that begins with general ill-health, loss of
appetite, nausea, vomiting, body aches, mild fever, dark urine, and
then progresses to development of jaundice. The illness lasts for a
few weeks and then gradually improves in most affected people. A
few patients may have more severe liver disease (fulminant hepatic
failure), and may die as a result of it.
2- The infection may be entirely asymptomatic and may go
unrecognized.
3- Chronic infection with hepatitis B virus may be either asymptomatic
or may be associated with a chronic inflammation of the liver
(chronic hepatitis), leading to cirrhosis over a period of several
years. This type of infection dramatically increases the incidence of
hepatocellular carcinoma (liver cancer). Chronic carriers are
encouraged to avoid alcohol as it increases their risk for cirrhosis
and liver cancer.
Transmission
Unprotected sexual contact, blood
transfusions, re-use of contaminated
needles & syringes, and vertical
transmission from mother to child during
childbirth.
• Diagnosis of Hepatitis B:• Detection of Hepatitis B surface Ag
• Detection of antibodies against Hepatitis B
surface Ag
• Detection of Hepatitis B core Ag
• Detection of antibodies against Hepatitis B
core Ag
Clinical Outcome Of Acute Hepatitis B
Hepatitis B Prevention
HBsAg VACCINATION
• a Recombinant vaccines, and plasma-derived vaccines are used;
• The two types of vaccines are equally effective and safe. Infants may
be vaccinated at birth.
• a Infants for infected mothers maybe immunized by antibodies to the
hepatitis B virus (hepatitis B immune globulin or HBIg) as well.
Treatment
• b Treatment is used for patients suffering from fulminant hepatitis or
chronic hepatitis or immunocompromised . to reduce the risk of cirrhosis
and liver cancer.
• a Acute hepatitis B infection doe^flotjusualjy require treatment
• because most adults cleajjfte infection spontaneously. a Antiviral drugs
and interferon alpha-2a:
Hepatitis A
Structure
• The Hepatitis virus (HAV) is a Picornavirus; it is non-enveloped and
contains a single-stranded RNA packaged in a protein shell.
Infections and Pathogenesis
•HAV infection does not lead to chronic or persistent hepatitis.
•Following ingestion HAV enters the bloodstream through the epithelium of
the oropharynx or intestine. The blood carries the virus to its target, the liver,
and multiplies within hepatocytes and Kupffer cells (i.e., liver macrophages),
Virions are secreted into the bile and released in stool; HAV is excreted in
large quantities approximately 11 days prior to appearance of symptoms or
anti-HAV IgM antibodies in the blood.
•The incubation period is 15-50 days.
•Mortality is less than 0.5%.
Diagnosis of Hepatitis A
• Detection of HAV-specific IgM
• Hepatitis A virus is present in the blood, (viremia), and feces of
infected people up to two weeks before clinical illness develops.
Prevention
• 1- Vaccination: The vaccine protects against HAV in more than 95%
of cases for 10 years. It contains inactivated Hepatitis A virus
providing active immunity against a future infection.
2- Good hygiene and sanitation.
Treatment
• There is no specific treatment for hepatitis A. Sufferers are advised
to rest, avoid fatty foods and alcohol, eat a well-balanced diet, and
stay hydrated.
Other Viral Hepatitis
HepC: majority of people are subclinical, 25% of infected people develop
acute hepatitis some of these develop liver cirrhosis and some of these
develop hepatocellular carcinoma.
• • Lab diagnosis: RT-PCR of viral RNA in blood of patients , antibody
detection.
• • Treatment; Interferon a and the antiviral drug ribavarin.
Hep D: Co infection with HepB.
• Its presence with HepB results in fulminant hepatitis, and in case of chronic
hepatitis it results in liver cirrhosis and cancer.
• Lab diagnosis: detection of delta antigen or IgM, or HDV in the serum
• of patients. Treatment: no vaccine follow HBV.
HepE.
• Infects mainly young adults and is sever in pregnant women, can lead
• to her death. No cnronicity.
• Lab Diagnosis: viral RNA detected in feaces of infected patients. No
treatment and no vaccine
Childhood viral diseases Measles (rubeola)
- Highly contagious infection of die respiratory system that is caused by a virus. a - Measles virus is Enveloped, SS, negative-sense RNA viruses.
- Transmission: aerosol transmission.
- IP. about 10 days. 3 or 4 days of fever, cough cold-like symptoms followed by a ,
rash recovery after 2 weeks of illness and life-long (immunity) to becoming infected
again.
• Complications from measles more commonly occur in children aged younger than 5
and adults older than 20. Serious complications of measles include blindness,
inflammation of the brain caused by infection (encephalitis), sever dehydration, ear
infections, and severe respiratory infections. The most common cause of death
associated with measles is from pneumonia. SSPE is a rare chronic, progressive
encephalitis .A history of primary measles infection usually before the age of 2 years
followed by several asymptomatic years (6-15 on average) and then gradual,
progressive psychoneurological deterioration, consisting of personality change,
seizures, myoclonus, ataxia, photosensitivity, ocular abnormalities, spasticity, and
coma. 1 jn 100,000 people infected with measles develop SSPE.
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No treatment only antipyretics .
German Measles(Rubella)
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Virus: enveloped icosahedral SS RNA.
IP 14-21 days followed by a
rash accompanied by fever 1-7 days
later.
German measles is usually a mild illness. However, if a
pregnant woman becomes infected, German measles
can cause Congenital rubella syndrome: deafness,
cataract and Congenital heart disease
• If the infection occurs 0-12 weeks after conception, there
is a 51% chance the infant will be affected. Problems
rarely occur when rubella is contracted by the mother
after 20 weeks of pregnancy.
• Vaccination against rubella:• MMR vaccin living attenuted vaccine
against rubella, measles and mumps
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Influenza virus
•SS, RNA Enveloped ,spherical virus that has its genome segmented into(&segments )
•Envelope carry two types of antigens :
H(heamagglutinin), N (neuraminidase). Variation in the H
and N results in antigenic shifts.
Transmission by respiratory droplets
Pathogenesis Acute disease that is characterized by:
chills, headache, extreme drowsiness, muscle aches and
fever.
Complications:
• pneumonia for the young and elderly or the immunocompromised.
• Reye syndrome: vomiting, brain dysfunction, coma and death . This syndrome was
related to the use of aspirin as antipyretic. Most affected are teenagers and children.
Treatment:
• amantadine, rimantadine prevent (inhibitors of
uncoating).
• Relnza and Tamiflu prevent release of the virus
from infected cells (inhibitors of release).
Prevention:
• vaccine made of formalin inactivated virus and
should contain the specific subtypes of the
influenza virus.
• Amantadin and rimantadin can be used as
preventive medication for risk groups.
Human Immune Deficiency Virus (HIV)
-Enveloped SS RNA icosahedral virus that contain reverse transcriptase_enzyme that
converts RNAto DNA.
Pathogenesis:•
pathology results from tissue destruction by the virus itself , or the host response
to_the virus jnfected cells.
HTV can induce a state of immunediffeciency that leads to opportunistic infection,
Treatment:
treatment regimens and immune supperssion can havs serious effect on
on gastrointestinal health. Cachexia (wasting syndrome) and diarrhea are a hallmark
of AIDS.
HIV Virus
AIDS : Acquired Immune Deficiency Syndrome
Stages in the HIV infection
• Category A: asymptomatic or swollen lymph nodes.
• Category B: persistant infections by Candida albicans
in mouth throat and vagina, Shingles, persistent
diarrhea, fever, cancerous or precancerous cervix. This
is a latent period that would last for months to years.
• Category C : Clinical AIDS Candida of esophagus,
bronchi, lungs, CMV eye infection pneumocystis
pneumonia, toxoplasmosis, Kaposi's sarcoma.
Progression to AIDS takes about 10 years in adults.
HIV Virus
Diagnosis:
• 1- CD4Tcells/mm3 a count below 200/mm3 is considered diagnostic.
• 2- seroconversion
• 3- Plasma viral load tests.
Treatment:
Highly active retroviral therapy HAART
Prevention:
• education
• No vaccine due to (high mutation rate\
• Treatment of pregnant mother and newborn, screening blood supply, strict
adherence to standard precautions by health workers.
Rabies Virus
SS, RNA,enveloped helical symmetry
Bullet shaped virus.
Transmission:
1- bite of a rabied animal
2-Aerosols from droppings of bats.
Symptoms:
Hallucination , seizures ,
weakness,paralysis,coma ,finally death
hydrophobia.
Once symptoms begins death is inevitable.
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Pathogenesis of Rabies
Treatment and prevention:
•If clinical symptoms appear there is ineffective
treatment.
•HDVC: Human Diploid Cell Vaccine preexposure
prophylaxis for people at high risk.
•Postexposure prophylaxis after the animal bite:
Clean the wound, passive immunization(RIG).
Active immunization (vaccine).
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Arbovirus(Arthropod borne viruses)
Transmission: through bite of mosquito.
-The virus can replicate in both humans and mosquito
-Mosquito bite is followed by viremia resulting in the
dissemination of the virus in target organ.
Majority of infections are subclinical but some show different
clinical syndromes:
- Encephalitis e.g. Japanese encephalitis virus JEV.
- Hemorrhagic fever e.g. yellow fever
- Fever myalgia and rash e.g. dengue virus (dengue hemorrhagic
fever)
Lab diagnosis: serologic acute and convalescent samples
Prevention: control the vector (Aedes aegypti) for dengue and yellow
fever. Vaccine for JEV"and yellow fever exist.
Rift Valley Fever
• Rift valley fever (RVF) is a viral zoonosis
that primarily affects anjmals but also has
the capacity to infect humans.
• Infection can lead to high rates of disease
and death in animals and humans.
• Disease also results in significant
economic losses due to death and
abortion among RVF-infected livestock.
Rift Valley Fever
Transmission:
- Direct contact between humans and blood or organs of infected
animals.
Virus enters human body through:
1- inoculation through broken skin.
2- inhalation of earosoles3uring slaughtering of infected animals.
3- Ingestion of unpasteurized or uncooked milk.
4- Bites of infected mosquitos (mostly Aedes aegyptis)
No human to Human transmission has been documented.
No evidence of RVF outbreaks in Urban aereas.
Rift Valley Fever
Pathogenesis:
- IP 2-6 days
- Subclinical or mild : feverish syndrome with sudden onset of flu-like
symptoms, muscle pain, joint pain and headache.
-Some patients develop neck stiffness, sensitivity to light, loss of
appetite (the disease may be mistaken for
Other forms of the disease:
ocular form,
menigioencephalitis form,
hemorrhagic fever form.
Diagnosis: IgM detection , cell culture, antigen detection by RTPCR.
Treatme&prevention: symptomatic inactivated vaccine,
Rota virus
-DS RNA non-enveloped it has the appearance of a
wheelTlnere are different strains of rotavirus and multiple
infections by different strains occur.
-It is the most common cause o^severe diarrheajamong
infants and children throughout the world and causes the
death of about 600,000 children worldwide annually.
-Most children become infected with rotavirus by a^e 3^'
Transmission(Fecal oral.infectious particles are stable
and can survive for long periods on surfaces
• Lab diagnosis:(Elisa& EM) for stool
Pathogenesis: IP is 48 hours. Infection could be
subclinical or result in mild diarrhe and vomiting to
sever non-bloody watery diarrhea that is accompanied
fever and vomiting dehydration and loss of
electrorytes.
Treatment and Prevention
•Rapid and efficient replacement of electrolytes and fluftfs that could
be sometime
•Rotavirus vaccine that is live attenuated vaccine
Enteroviruses
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SS RNA non-enveloped viruses
Transmission : Fecal-Oral.
-Stable in the low pH of the stomach, replicate in the gastrointestinal
tract and is excreted in the stool of patients.
- Leave the GIT to the blood stream and spread to various organs.
enterovjruses can cause CNS diseases they are major causes of
aseptic meningitis.
-Viral meningitis occur mainly in summer and fall.
- Affect both children and adults.
Treatment: Symptomatic. No antiviral
Poliovirus is an enterovirus.
-Prevention is(by vaccination)
-Vaccines : attenuated(Sabin), or killed(Salk)
Common cold viruses
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Viral upper respiratory tract infection
is a self-limited contagious illness
that can be caused by any of 200 different types of viruses. Because of this
the body never builds up resistance against all of them. Thus colds are a
frequent and recurring problem.
Symptoms: runny_nose or scratchy throat fever and headache. Symptoms
last for 10 days.
Transmission: direct hand-to-hand contact with infected secretions or from
contaminated surfaces.
Pathogenesis: virus replicate at nasal passages because it requires low
temperature.
Treatment: Supportive measures for the common cold include rest and
drinking-plenty of fluids. Over-the-counter medications such as throat
lozenges throat sprays, cough drops, and cough syrups may also help
bring relief Decongestants such as pseudoephedrine (Sudafed) or
antihisiamines may be usect-for nasal symptoms. Saline sprays and a
humidifier may also be beneficial.