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VIROLOGY Positive (+) RNA Viruses SAMUEL AGUAZIM M.D. Lange Chapter 40 Definition of Positive (+) RNA Viruses Viruses whose genomic RNA either can serve directly as mRNA (all + RNA viruses except the retroviruses) OR has the same sequence as the mRNA (retroviruses) Characteristics of (+) RNA Viruses Naked (+) RNA is infectious Positive RNA Viruses (except retroviruses) replicate in the cytoplasm No (+) RNA virus is segmented The retrovirus are diploid (two copies of the chromosome) Most RNA viruses are Enveloped. The exception are the smallest-the caliciviruses and picornaviruses. Family Picornaviridae Small, naked viruses with +RNA genome. Two major groups Enteroviruses – Acid stable, infect GI tract mainly transmitted feco-orally Polio viruses (Type 1,2 & 3) Coxsackie viruses A (21 serotypes) B (6 serotypes) ECHO viruses (34 serotypes) New enteroviruses (strain 68,69,70,71 & 72) Rhinoviruses – Acid labile, infects upper respiratory tract, transmitted by inhalation of droplets. Family Picornaviridae (Enteroviruses) Poliovirus Echovirus Enteroviruses 68-71 Coxsackievirus A & B Rhinoviruses Hepatitis A (mnemonic: PEECoRnA) Table 3 Properties of Rhino- and Entero-viruses Optimum Site of pH Detergent Sero Transgrowth primary sensitivity sensitivity types mission temperature infection Rhino labile to viruses acid pH 33 degrees C (approx) Entero resistant to 37 degrees viruses acid pH C (approx) >100 aerosol Resistant 72 upper respiratory tract oro-fecal gut Genera that infect humans Enterovirus Polio Coxsackie A and B Echo Other enteroviruses Diseases of the human (and other) alimentary tract (e.g. polio virus) Rhinovirus Disease of the nasopharyngeal region (e.g. common cold virus) Hepatovirus Human hepatitis virus A Parechovirus Formerly echoviruses 22 and 23. Disease of alimentary and respiratory tract Table 4 Human diseases caused by enteroviruses Poliovirus Coxsackie A virus Coxsackie B virus Echovirus Enterovirus (other) Asymptomatic infection yes yes yes yes yes Meningitis yes yes yes yes yes Paralysis yes yes yes yes no Febrile exanthems no yes yes yes yes Acute respiratory disease no yes yes yes yes Myocarditis no yes yes yes no Orchitis no no yes yes no POLIO case A 6 year old child, female, developed flulike illness, and was managed symptomatically. 10 days later, she developed weakness of her left leg, which progressed to complete paralysis. Sensation was normal. The other extremities were normal. Respiration was also normal. case She was diagnosed with a viral illness, and underwent a series of physical therapy, however, the affected limb became shorter and smaller. Surgery was done to facilitate mobility. CASE Impression: Poliomyelitis Poliovirus Transmission is fecal-oral Close to being eradicated through the use of the oral (attenuated) Sabin or the killed (Salk) vaccines. Virus infects oral and gastrointestinal epithelium >90%of the infections are asymptomatic When the virus infects the anterior horn cells of the spinal cord (1in 250 infections), poliovirus may cause a paralytic disease involving the cranial and respiratory nerves. POLIOVIRUS: Most infections (greater than 90%) are asymptomatic, disease may appear as: a. Abortive poliomyelitis: (minor illness) The first symptomatic result of polio infection is febrile disease (fever) and occurs in the first week of infection. The patient may exhibit a general malaise which may be accompanied by vomiting, a headache and sore throat. b. Nonparalytic poliomyelitis: Three or four days later a stiff neck and vomiting, as a result of muscle spasms, may occur in about 2% of patients. The virus has now progressed to the brain and infected the meninges. c. Paralytic poliomyelitis: In bulbar paralysis cranial nerves and the respiratory center in the medulla are affected leading to paralysis of neck and respiratory muscles. There is no sensory loss associated with the paralysis. The degree of paralysis may increase over a period of a few days and may remain for life or there may be complete recovery over period of 6 months to a few years. In bulbar poliomyelitis, death may also ensue in about three quarters of patients, especially when the respiratory center is involved. Patients were able to survive for a while using an iron lung to aid respiration (figure 4). figure 4 .Paralyzed child in an iron lung Child with polio © WHO Live (Sabin) vaccine: 1. Advantages: induces secretory antibody response (IgA) in addition to IgG; oral delivery easily administered; long duration of immunity; indirect immunization in community by circulation of attenuated vaccine virus; eliminates circulation of ‘wildtype’ polio. 2. Disadvantages: vaccine associated polio in vaccine recipients and contacts; reversion of virus to virulence; requires refrigeration; unsafe for immunodeficient patients. Inactivated (Salk) vaccine: 1. Advantages: No risk of poliomyelitis in vaccinees or contacts; incorporated into routine immunizations (DPT); good stability in storage and transport; safe for immunodeficient patients; no concern about reversion. 2. Disadvantages: No local immunity in gut; doesn’t stop circulation of wild-type polio therefore need high levels of community immunization; injection more expensive than oral administration; need booster doses. POLIOVIRUS VACCINE: Current practice in the United States is to give: four immunizations of the inactivated vaccine One booster if you travel to endemic areas. The inactivated vaccine induces antibodies, which can prevent virulent revertants in the live vaccine from causing paralytic poliomyelitis. Immune globulins are available but rarely used. Echovirus: Enteric Cytopathogenic Human Orphan viruses Highly infectious, and its primary target is children. The echovirus is among the leading causes of acute febrile illness in infants and young children most common cause of aseptic meningitis. Infection within the first two weeks of birth can cause devastating and potentially fatal disease. In this population, death usually results from overwhelming liver failure or myocarditis, rather than infection of the central nervous system. can mimic symptoms caused by other common bacterial and viral infections, so echovirus infections are often treated with therapies aimed for other infections. evolution of antibiotic resistant bacteria. Main causes of infection are from overcrowded conditions such as the poor districts of a city and poor hygiene. Occurs disproportionately in males Other Enteroviruses Enterovirus 70 is the causative agent epidemics of acute haemorrhagic conjunctivitis that swept through Africa, Asia, India and Europe from 1969 to 1974. The virus is occasionally neurovirulent. Enterovirus 71 appears to be highly pathogenic and has been associated with epidemics of a variety of acute diseases, including aseptic meningitis, encephalitis, paralytic poliomyelitislike disease and hand-foot-mouth disease. Enterovirus 72 is the designation assigned to hepatitis A virus ACUTE HEMORRHAGIC CONJUNCTIVITIS Coxsackie Virus A (mainly serotype A 16) cause herpangina(fever, sore throat and tender vesicles in the oropharynx). Hand, foot, and mouth disease(painful blisters in the mouth, throat, hands, feet, or in all these areas). is the common name of this viral infection. Aseptic Meningitis Acute lymphoglandular pharyngitis Common cold usually occurs in children, but adults can also develop the condition. should not be confused with the “foot and mouth disease" usually found in animals with hooves (for example, cattle, pigs, and deer). Type A also causes conjunctivitis (inflammation of the eyelids and white area of the eye). Hand, Foot and Mouth Disease Hand, Foot and Mouth Disease Coxsackie Virus B Bornholmes disease (a.k.a, pleurodynia or Devil’s grip; severe intercostal pain and fever in many areas. Sufferers of chest pain should see a doctor immediately myocarditis or pericarditis, which can result in permanent heart damage or death. Aseptic Meningitis As a group, they are the most common cause of unexpected sudden death, and may account for up to 50% of such cases. illness may last for up to two weeks, but may resolve as quickly as two days. Infection usually occurs between the months of June and October. Rhinovirus Major causative agent of the common cold Over 100 serotypes The cell surface receptor is ICAM-1. Transmission: Respiratory Peak in the summer and early fall Not resistant to stomach acid Grows 33 degrees Celsius Family Caliciviridae Norwalk Agent Gastroenteritis -”a.k.a Norovirus” - Noninflammatory diarrhea found in older children and adults. - Fecal-oral in shellfish food or water - 1-2 day incubation and 1 day of vomiting, diarrhea and low grade fever. Hepatitis E – see Hepatitis lecture Family Flaviviridae - Are enveloped,icosahedral (+) RNA viruses (Flavi means “yellow”) Hepatitis C – see lecture on hepatitis viruses Yellow Fever Virus Dengue Virus ( Mc) St. Louis Encephalitis Virus West Nile Virus Yellow Fever Virus Tropical South America and Africa Spread by mosquitoes Arthropod-borne virus = arbovirus Febrile disease of varying severity Often includes hepatitis and may progress to hemorrhagic fever( Fever plus Black Vomitus) Liver Biopsy Reveals COUNCILMAN BODIES Live Attenuated vaccine Dengue Virus (breakbone disease) Arbovirus Spread by the Aedes mosquitoes in the tropics, including the Gulf Coast of the United States. Rapid onset, with fever, severe myalgias, arthralgias, headache, and rash. Four serotypes Dengue hemorrhagic shock syndrome (DHHS) is a serious complication seen in young babies with maternal antibodies or in any individual with antibody from a previous infection who is infected with a second dengue serotype. St. Louis Encephalitis Virus Spread by the Culex mosquito endemic in Canada, the South Eastern United States , the Caribbean, and South America. Most severe in the elderly often present with global brain involvement such as tremors and cranial nerve dysfunction. St. Louis and West Nile encephalitis are the two most common causes of arboviral encephalitis. West Nile Virus Spread to the western hemisphere in 1999 most commonly diagnosed arbovirus in the United States now a major mosquito-borne infection of birds, horses and humans Thousands have been infected but deaths have occurred mainly in the debilitated elderly persons. In addition to the encephalitis, there may be muscle weakness and flaccid paralysis Family Togaviridae Enveloped, icosahedral Western, Eastern, and Venezuelan equine encephalitis viruses, Chikungunya WEE: is most prevalent to western and central United States and Canada. EEE: is most prevalent in swampy areas of the United States eastern coast. VEE: most prevalent in Venezuela, Colombia, Central America, and Texas. Rubella Virus “German Measles” Western, Eastern, and Venezuelan equine encephalitis viruses Horses are the dead-end hosts Wild Birds are the normal hosts Mosquitoes transfer the disease to humans Disease: Encephalitis Presentation Headache Nausea Vomiting, fever Changes in metal status ( confusion, stupor) Rubella Virus “German Measles” or 3-days Measles transmission: respiratory droplets and transplacentally Discrete red maculopapular rash Mild fever Can cross the placenta and cause serious birth defects, such as cataracts, patent ductus arteriosus and Sensorineural deafness(known as the Rubella Triad). Vaccine MMR (measles, mumps & Rubella) is a single attenuated strain of rubella virus. Recommended that barrier protection be used to prevent pregnancy for 16 weeks after vaccination. maculopapular rash beginning on the face and spreading to the extremities. Infant with congenital rubella syndrome. The common clinical presentation in pregnant women infected with rubella during the first trimester includes a maculopapular rash along with postauricular and suboccipital lymphadenopathy. Congenital rubella occurs when a pregnant woman is infected with rubella during the first trimester, and the virus infects fetal cells transplacentally For normal lab values: http://www.usmle.org/step1/2005Step1.pdf Coronavirus First isolated from chickens in the 1930s, coronaviruses are known to be pathogenic for many animal species. Outbreak of coronavirus pneumonia (CVP), also known as Severe Acute Respiratory Syndrome (SARS) in February 2003. Researchers at Hong Kong University recently identified a new coronavirus as the cause. Structure: Spherical or pleomorphic enveloped particles containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. The envelope bears club-shaped glycoprotein projections. Two serotypes called ( 229E & OC43) Receptor for SARS( angiotensin-converting enzyme-2) SARS Virus Transmission: enters the body through the eyes, nose and mouth. An important route seems to be touching objects that are contaminated with viruses. Close person to person contact seems important for efficient spread. gets their name from their striking corona (crown) of spikes made of S glycoprotein. These spikes bind to host cells and allow the virus to enter the cell. The virus is enveloped SARS Virus The spike Symptoms of SARS: begins with a fever (measured temperature greater than 100.4°F [>38.0°C]). chills or other symptoms, including headache, general feeling of discomfort and body aches. Some people also experience mild respiratory symptoms at the outset. After 2 to 7 days, SARS patients may develop a dry, nonproductive cough that might be accompanied by difficulty breathing and atypical pneumonia. SARS: Diagnosis/Evaluation Initial diagnostic testing for suspected SARS patients should include: chest radiograph pulse oximetry blood cultures sputum Gram's stain and culture Testing for viral respiratory pathogens, notably influenza A and B and respiratory syncytial virus. A specimen for Legionella and pneumococcal urinary antigen testing should also be considered. For individuals who must travel to a SARS-affected area: CDC advises that travelers in a SARSaffected area should wash their hands frequently to protect against SARS infection. In addition, CDC advises that travelers may wish to avoid close contact with large numbers of people as much as possible to minimize the possibility of infection. For individuals who think they might have SARS: People with symptoms of SARS (fever greater than 100.4°F [>38.0°C] accompanied by a cough and/or difficulty breathing) should consult a health-care provider. To help the health-care provider make a diagnosis, tell them about any recent travel to places where SARS has been reported or whether there was contact with someone who had these symptoms VIRUS FAMILY RNA VIRION STRUCTUR ASSOCIAT E ED POLYMER ASE ENVELOPE SHAPE REPLICAT E IN MAJOR VIRUSES calici Ss+RNA linear non segmented No Naked Cytoplasm norwalk Hepe virus “”””’’’’’ “”’’’ Picorna “””””’’’ “””””””””””””” Icosahedral Hep E “””””””””””” “”””””””””””” “”””””””””” Polio Echo Enterovirus Coxsackie Hep A VIRUS FAMILY RNA VIRION STRUCTUR ASSOCIAT E ED POLYMER ASE ENVELOPE SHAPE REPLICAT E IN MAJOR VIRUSES Flavi Ss+ RNA linear nonsegmented No Enveloped Icosahedral Cytoplasm Yellow fever, dengue, SLE , hep c Toga-virus “”””””””””””” “””””””””””” “”””””””””” “””””””””” “””””””””” Rubella. WEE. EEE,VEE CORONA “””””””””” “””””””””””” “”””””” HELICAL “”””””””””” CORONA RETRO DIPLOID Ss+RNA LINEAR nonsegmented Yes, RNA DEPENDE NT DNA POLYMER ASE “”””””””””””” ICOSAHED NUCLEUS RAL OR TRUNCATE D HIV’ HTLV. SARCOMA