TRANS 1 : RABIES Rabies: Rhabdo virus, bullet shaped, enveloped, G, matrix main problem: animal reservoirs _________________________________________________ STRUCTURE:

-enveloped, peplomer (glycoprotein- trimers of viral gp) -helical neuclocapsid - (-) ssRNA + for RNA-dep RNA polymerase >G protein: glycoproteins w/c are targets of neutralizing Ab >M protein: matrix protein w/c lines the inner surface >nucleocapsid: helical infectious core >L protein & NS protein: RNA polymerase/transcriptase 60% of genome _________________________________________________ CLASSIFICATION: Family: Rhabdoviridae Genus: Lyssavirus -widely distributed in nature & man is only an accidental host -it doesn't affect insects _________________________________________________ SUSCEPTIBILITY >very high >high >moderate >low : : : : canines (wolves, jackals, foxes, coyotes) rodents (hamsters, skunks, racoons,) canines, felines, cattle oppposums

_________________________________________________ Ag'ic PROPERTIES - 1 serotype but but it has different strains - G glycoprotein : neuroevasiveness & pathogenicity - peplomers elicit neutralizing Ab in animals _________________________________________________ REACTIONS TO AGENTS - can survive more in below freezing temp (-70deg) for years - easily inactivated by CO2, UV, sunligh, lipid solvents, detergents _________________________________________________

REPLICATION virus attachment/fusion (via peplomers) forms an endosome core is released in the cytoplasm nucleocapsid is uncoated viral (-)ssRNA is transcribed to a (+)ssRNA (+)ssRNA serve as a template for synthesis of viral genome & proteins - (-)ssRNA incorporated into the nucleocapsid - join the matrix protein at the cell surface - will be released through budding off the cell surface BINDING -> PENETRATION -> TRANSCRIPTION -> REPLICATION -> ASSEMBLY G-M ssRNA-L&NS _________________________________________________ PATHOGENESIS rabies replicates at site of inoculation spread through nerves until it reaches the CNS peripheral nerves salivary glands & tissues multiple organ damage: kidney, heart, pancreas, retina, cornea

mRNA for

*isolated from: submaxillary salivary gland, blood _________________________________________________ Manifestations & Diagnosis >CANINE RABIES 1. Furious type - viciousness & aggresiveness, biting aimlessly and at inanimate objects, mouth foaming, hydrophobia (difficulty in eating and drinking), restlessness 2. Dumb type - lethargic animal, occurs more commonly in cats, animals hide in dark, silent p laces; sluggish and sleepy - paralysis; no hydorphobia, tongue is usually hanging while the animal salivate s continuously -animal dies with no signs >HUMAN RABIES 1. Short, Prodromal stage - 2-3 days; NON-SPECIFIC signs: fever, nausea, appetite loss - ANS is affected as shown by copious salivation & sadness 2. Anger stage

- 2-3 days - irritability, restlessness, and aggression - seizures 3. Neurologic, Paralytic stage - 2-4 days - paralysis develops usually at the site of the bite - hydro-, aerophobia, uncontrolled movement, paralysis of throat and face _________________________________________________ LAB DIAGNOSIS Gold Standard of FAT 1. Viral Isolation - available tissue is inoculated intracerebrally into suckling mice - encephalitis & death- (+) for rabies (2-4 days) - Negri bodies (magenta), rabies Ag - too long for decision making as to whether give vaccine/not 2. Serology - immunofluorescence & neutralization tests are done for the detection of Ab in the serum - Ab develop slowly in serum of infected persons 3. Animal Observation - usually takes 10 days: do not immediately kill (cull) suspected rabies-positiv e dogs 4. Electron Microscopy - Negri bodies are searched through Seller's stain - also can be seen in the blood !!! FAT _________________________________________________ RABIES DIAGNOSIS IN ANIMALS: ! postmortem only because there is no reliable antemortem test - FAT should be done in fresh brain samples so it should be kept in freezing tem peratures _________________________________________________ RABIES DIAGNOSIS IN HUMANS: - can only be diagnosed when symptoms has manifested ! serology cannot be done because Ab are produced later in the disease or after vaccination ! saliva isolation ! skin biopsy (+) early in the disease through FAT _________________________________________________ TREATMENT & PREVENTION

*People at risk- constant exposure to animals, pet owners *Pre-exposure: 3 vaccines: 0, 7, 21 days *Post-exposure: > never vaccinated- 5 vaccines: 0, 3, 7, 14, 28 with HRIG at site of wound > vaccinated- 2 vaccines: 0, 3 no HRIG _________________________________________________ IMMUNITY & PREVENTION Cat. 1 - no vaccine Cat. 2 - vaccine & wound cleaning Cat. 3 - vaccine, HRIG, local wound treatment _________________________________________________ !!! CAN be given to PREGNANT women