10. rabies

what shape are rhabdoviridae? are they naked or enveloped viruses?

• bullet shaped

• enveloped

what type of genome do rhabdoviridae have?

non-segmented RNA

what 5 structural proteins are encoded in the genome?

• N: nucleocapsid

  • encapsulates genome; forms ribonucleocapside (RNP)

• P: phosphoprotein

  • cofactor for polymerase

• M: matrix protein

• G: glycoprotein

  • binding

• L: polymerase

  • stuttering (?)

what are the general steps in the virus’s life cycle?

1. attachment: receptor/virus interaction

2. virus entry: G protein

3. uncoating and RNP release

4. transcription

5. replication (genomic RNA)

6. assembly: M protein

7. budding or release

what is a reservoir host?

host that is capable of sustained intra-species maintenance of a variant within a geographic area (maintain viruses in population)

• not “sub-clinical” or chronic shedders

how is a susceptible host different from a reservoir host?

susceptible hosts do not maintain viruses in the population → infection ends in host

what factors influence rabies incubation period?

• severity of exposure

• proximity to brain

• species of animal

• variant of virus

how does rabies spread throughout the body?

nerves innervating skeletal muscles → travels up CNS to brain → spread along nerves to salivary glands, skin, cornea & other organs

what are the two forms of rabies?

• furious: aggressive, unprovoked attacks

• paralytic (aka “dumb”): depressed

what demographic makes up a large portion of fatal human rabies cases?

children under 15 years old (~40%)

(outside of the US) what is the main source of rabies transmission to humans?

dogs

what is the main source of rabies in the US?

wild mammals (bats, raccoons, skunks, foxes, etc.); mongooses (in Puerto Rico)

how is a direct fluorescent antibody test (DFAT) used to diagnose rabies?

• microscopic detection of viral antigens using a fluorescent conjugate with antibodies to RABV

• test brain tissue

• gold standard for rabies testing

• diagnostic for rabies

how is immunohistochemistry used to diagnose rabies?

• detects RABV antigens

• similar sensitivity as DFAT

• can use formalin-fixed tissues

what are negri bodies? how are they interpreted diagnostically?

• inclusion bodies where viral replication and assembly happens during infection

• histopathologic signature of rabies but NOT definitive for diagnosis (highly suggestive)

how is a rapid fluorescent focus inhibition test (RFFIT) used to diagnose rabies?

• detection of neutralizing antibodies using live RABV, cell culture, and fluorescent conjugates

  • positive = neutralizing antibodies present; no cell infection

  • negative = no antibodies present; cells infected

• (important for rabies testing)

how is RT-PCR used to diagnose rabies?

• can be used for diagnosis and characterization of lyssaviruses (rabies genus)

• useful when samples are not suitable for DFAT

• primer targets usually for N gene (most conserved)