negative (-) single-stranded rna viruses samuel aguazim m.d. lange chapter 39

NEGATIVE (-) SINGLE-STRANDED RNA VIRUSES SAMUEL AGUAZIM M.D. Lange Chapter 39

FAMILIES AND DISEASES Paramyxovirus Parainfluenza, Respiratory Syncytial Virus, measles (Rubeola), Mumps, Rhabdoviridae Rabies Virus Filoviridae Ebola and Marburg viruses Orthomyxoviridae - Influenza A and B Viruses

HIGH YIELD CONCEPTS Negative Sense RNA, abbreviated (-) RNA is the homolog of mRNA All (-) RNA Viruses carry a virion-associated, RNA- dependent RNA polymerase Naked (-) RNA (i.e., without the RNA dependent RNA polymerase protein) is not infectious. All (-) RNA Viruses are helical and enveloped. No (-) RNA viruses are naked or icosahedral. Three families of (-) SS RNA Viruses are segmented: Orthomyxoviridae, Bunnaviridae, and Arenaviridae

Myxoviruses Orthomyxo viruses Paramyxo viruses - Smaller - Segmented RNA genome - Liable to Ag variation - Larger - Single piece of RNA - Not liable to Ag variation Influenza viruses - Parainfluenza - Mumps virus - Measles virus - Respiratory syncytial virus Myxo = affinity to mucin

INFLUENZA VIRUSES Replicate in mucus membranes Target tissue: upper & lower respiratory tract Cause influenza : acute respiratory disease that may occur in epidemics or even pandemics

FAMILY ORTHOMYXOVIRIDAE- INFLUENZA A & B Segmented (8) Separate H ( hemaglutinin) and ( neuraminidase) Glycoproteins Can lead to Guillain Barre (A or B) or Reyes syndrome (primarily B) Inactivated vaccine, H1N1 and H3N2 Influenza A & B (also HIV) undergoes genetic drift = slight changes in antigenicity due to mutations (responsible for epidemics) Influenza A has a rare genetic shift Vaccine contains 2 A strains and one B strain: Reformulated every year

Influenza: ORTHOMYXOVIRUSES M1 protein helical nucleocapsid (RNA plus NP protein) HA - hemagglutinin polymerase complex lipid bilayer membrane NA - neuraminidase M2 Protein

Haemagglutinin Binds to host cell surface receptor The target of neutralizing Abs Haemagglutinates RBCs from various animal species Neuraminidase Cleaves neuraminic acid to release virus progeny from infected cells Degrades the protective layer of mucin in the respiratory tract Plays a min role in immunity to influenza

Haemagglutinin Binds to host cell surface receptor Neuraminidase Cleaves neuraminic acid to release virus progeny from infected cells

INFLUENZA VIRUS: ANTIGEN DRIFT ANTIGENIC DRIFT Minor changes based on mutation in the genome RNA. Drift variants occur every year HA and NA accumulate mutations immune response no longer protects fully sporadic outbreaks, limited epidemics Influenza B undergoes drift but not shift ANTIGENIC SHIFT Major changes based on the reassortment of segments of the genome RNA new HA or NA proteins Occur every 10 or 11 years pre-existing antibodies do not protect may get pandemics

WHERE DO NEW HA AND NA COME FROM? 13 types HA 9 types NA all circulate in birds, pigs, avian and human

hemaglutinin Different hemaglutinin Influenza Virus Antigenic Shift

CLINICAL PICTURE INCUBATION PERIOD: 1-4 DAYS. Sore throat headache cough FEVER pneumonia and respiratory failure Reye,s Syndrome Complications 50% of infected people dont present any symptoms But still contagious This makes it difficult to stop the spread of the disease

INFLUENZA VIRUS IS LINKED TO REYES SYNDROME AND GUILLIAN-BARR SYNDROME Reyes syndrome liver - fatty deposits brain - edema vomiting, lethargy, coma risk factors youth certain viral infections (influenza, chicken pox) Aspirin Guillian-Barr syndrome Most common acute paralysis in the United State Ab will form against myelin protein Demyelination 1976/77 swine flu vaccine 35,000,000 doses 354 cases of GBS 28 GBS-associated deaths recent vaccines much lower risk

INFLUENZA A PANDEMICS

INFLUENZA VIRUS: VACCINE Killed influenza A and B viruses, typically two A strains and one B strain. The two A strains are recent H1Nl and H3N2 isolates. The vaccine is usually reformulated each year to contain the current antigenic strains. Because the virus is killed, there is no replication in the respiratory tract and, consequently, little secretory IgA appears on the respiratory mucosa. The vaccine does induce IgG, which offers some protection. The vaccine is not a good immunogen, because little IgA is made and the titer of IgG is relatively low. Protection lasts only 6 months. Yearly boosters are recommended and should be given shortly before the flu season, e.g., in October. Boosters provide an opportunity to immunize against the latest antigenic changes. The vaccine should be given to people older than 65 years of age and to those with chronic diseases, particularly respiratory and cardiovascular conditions. In 1994, the vaccination recommendations were expanded to include all persons who want to reduce their risk of acquiring influenza

II- CHEMOPROPHYLAXIS 1)Amantadine & Rimantadipne : Prevent penetration & uncoating of the virus Treat & prevent influenza A only Given to high risk groups 2) Zanamavir & Oseltamivir (tamiflu) They are neuraminidase inhibitors, inhibiting the release of virus from infected cells This limits the infection by reducing the spread of virus from one cell to another For treatment not prevention Effective against influenza A &B

INFLUENZA VIRUS True influenza influenza virus A worldwide epidemics influenza virus B major outbreaks influenza virus C infections - much milder, does not cause outbreaks recently some increase in morbidity and mortality - possible factors? more elderly people more high risk neonates more immunosuppressed patients INFLUENZA VIRUS CDC WEBSITE http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm

FAMILY PARAMYXOVIRUS Enveloped Helical nucleocapsid Negative sense ssRNA Fusion surface proteins Medical Important Virus Parainfluenza virus Respiratory Syncytial Virus (RSV) Mumps Virus Measles Virus (Rubeola)

CASE 2 year old female child, with fever for three days, accompanied by cough, coryza and conjunctivitis. Fever was high grade, which the mother managed with sponge baths and Paracetamol. A reddish rash was later noted on the childs face, spreading to her trunk and extremities. The child found it difficult to sleep, since the rashes were itchy.

CASE On PE, the temperature was 40C, with harsh breath sounds, no rales or wheezes. There was maculopapular rash, with some areas being reddish in color, while others were brownish.

CASE Maculopapular rash which extends from face to the extremities

CASE: CONJUNCTIVITIS

CASE: KOPLIK SPOTS small (1 - 3mm), irregular, bright red spots, with bluish-white speck at center opposite the upper 2 nd molars

CASE: IMPRESSION: Measles, uncomplicated TREATMENT : SUPPORTIVE

PATHOGENESIS & CLINICAL PICTURE Replication initially in the upper & lower respiratory tract Followed by LNs replication Viremia & growth in a variety of epithelial tissue Incubation period : 1-2 wks In 2-3 days, no rash but fever, running nose, cough & conjunctivitis

MEASLES VIRUS (RUBEOLA) Symptoms generally the three Cs with photophobia Cough, coryza and conjunctivitis Koplik spots: grey-white spots with a red base on the oral mucosa Rare Complication: subacute sclerosing panencephalitis Erythematous maculopapular rash which starts on the face and moves down. (rash results from the action of cytotoxic T cells on infected cells in the microcapillaries. Live attenuated vaccine (MMR) Pneumonia ( Warthin-Finkeldy cells)

M protein helical nucleocapsid (RNA plus NP protein) HA glycoprotein (1) SPIKES polymerase complex lipid bilayer membrane F glycoprotein (2) SPIKES pleomorphic MEASLES

MEASLES RASH

KOPLIK SPOTS

2-Koplick spots 3-Maculopapular rash 4-Skin exfoliation Persist 1-3 days Disappear after the rash onset Lasts for 3-7 days 1-Respiratory symptoms 2-3 days Long life immunity due to IgG neutralizing Abs

The virus invades the body via blood vessels reaches surface epithelium first in the respiratory tract where there are only 1-2 layers of epithelial cells Then in mucosae (Koplik's spots) and finally in the skin (rash).

CLINICAL CONSEQUENCES OF MEASLES VIRUS INFECTION Disordersymptoms Measles Characteristic maculopapular rash, cough, conjunctivitis, coryza, photophobia and kopliks spot Complication Otitis media, croup, bronchopneumonia and encephalitis ATYPICAL MEASLES RASH( most prominent in distal area) possible vesicles, petechiae, purpura or urticaria Subacute sclerosing panencephalitis Central nervous system manifestation(e.g personality, behaviour and memory changes, myoclonic jerks, spasticity and blindness

MUMPS VIRUS Causes epidemic parotitis ( non suppurative inflammation of parotid) Mode of transmission: Via aerosols & fomites The virus is secreted in urine so urine is a possible source of infection saliva

PATHOGENESIS & CLINICAL PICTURE Infects children 5-15years Replicates in the nasopharynx &regional LNs Incubation period: 2-25 d viremia Lasts 3-5 d meninges glands -Salivary -Pancreas -Testes -ovaries Long life immunity due to IgG neutralizing Abs

M protein helical nucleocapsid (RNA plus NP protein) H/N glycoprotein SPIKES polymerase complex lipid bilayer membrane F glycoprotein SPIKES pleomorphic MUMPS

Live attenuated Vaccine Aseptic Meningitis Orchitis in postpubertal males (rarely causes sterility except if bilateral) Parotitis Pancreatitis ***Memory Tool MOPP

HUMAN PARAINFLUENZA VIRUSES(1,2,3,4) HPIVs are second to RSV as a common cause of lower respiratory tract disease in young children Similar to RSV, HPIVs can cause repeated infections throughout life, usually upper respiratory tract illness Can also cause severe lower respiratory tract infections among immunocompromised patients

Each of the four HPIVs has different clinical & epidemiologic features The most distinctive clinical feature of HPIV-1& HPIV-2 is croup HPIV-3 is more associated with bronchiolitis & pneumonia HPIV-4 is infrequently detected, because it is less likely to cause severe disease Croup (laryngotracheobronchitis difficulty in breathing, hoarseness and a seal bark-like coughing

DIAGNOSIS OF CROUP Chest radiograph depicting subglottic narrowing, commonly called the "steeple sign.

RESPIRATORY SYNCYTIAL VIRUS Commonest cause of bronchitis & pneumonia among infants< 1yr. Causes repeated infections throughout life, usually associated with moderate- to severe cold like symptoms Severe lower respiratory tract disease may occur at any age, espec i ally elderly & those with compromised cardiac, pulmonary or immune systems

M protein helical nucleocapsid (RNA plus NP protein) polymerase complex lipid bilayer membrane F glycoprotein SPIKES: Ab against F, neutralizes infectivity RESPIRATORY SYNCYTIAL VIRUSES Pleomorphic: vary in shape Syncytia = multinucleated giant cells F=fusion

FAMILY RHABDOVIRIDAE RABIES VIRUS Bullet Shaped Negri Bodies intracytoplasmic inclusion bodies Prevention: Inactivated vaccine; passive immunization Spread to humans by bites of Rabid dogs; contact with bats Eastern U.S. reservoirs: foxes & raccoons; western U.S.: skunks

TRANSMISSION BITE - USUAL ROUTE CORNEAL AND OTHER TRANSPLANTS MUCOSAL MEMBRANES, WOUND AEROSOL (RARE)

RABIES PATHOGENESIS Virus is transmitted via bite Agents are highly neurotropic Enter peripheral nerves Centripetal travel by retrograde flow in axoplasm of nerves to CNS Replicate in brain Centrifugal flow to innervated organs, including the portal of exit, the salivary glands Viral excretion in saliva

Murray et al., Medical Microbiology Note: No Viremia

CLINICAL STAGES Incubation Period (range = ~ 6 years; average is ~4-6 weeks) Prodromal Phase (Non- specific signs) Acute Neurological Phase Coma Death (recovery from rabies?)

SYMPTOMS Variable, often misdiagnosed Tingling, paresthesia at bite site Fever, headache, malaise, anorexia Nausea, vomiting, myalgia, hydrophobia Confusion, hallucinations, seizures, paralysis Coma, respiratory failure, death

CLINICAL PRESENTATION Furious Rabies Headache, fever, irritability, restlessness and anxiety. muscle pains, salivation and vomiting. After a few days to a week the patient may experience a stage of excitement and be wracked with painful muscle spasms, triggered sometimes by swallowing of saliva or water. Hence they drool and learn to fear water (* Hydrophobia). The patients are also excessively sensitive to air blown on the face. The stage of excitement lasts only a few days before the patient lapses into coma and death. Once clinical disease manifests, there is a rapid, relentless progression to invariable death, despite all treatment.

CLINICAL PRESENTATION Dumb Rabies Starts in the same way, but instead of progressing into excitement, the subject retreats steadily and quietly downhill, with some paralysis, to death. Rabies diagnosis may easily be missed.

POST-EXPOSURE PROPHYLAXIS FOR RABIES After an animal bite, treatment consists of - one dose of rabies immune globulin - five doses of rabies vaccine over a 28-day period. Rabies immune globulin and the first dose of rabies vaccine are administered as soon as possible after you've been exposed and have reported the exposure to your doctor. You're given the immune globulin by injection around the site of the bite, and you receive injections of the vaccine into your upper arm muscle.

FAMILY BUNYAVIRIDAE California Encephalitis Virus - Mosquito Borne - young (

negative (-) single-stranded rna viruses samuel aguazim m.d. lange chapter 39

Documents