HIV/Rabies/PoxViruses Flashcards
What is the structure of HIV?
enveloped retrovirus (2xidentical +RNA) in the lentivirus family. contains reverse transcriptase, integrate & protease.
What is the general replication strategy of HIV?
attachment, co-receptor binding, fusion, reverse transcription RNA –> DNA, integration into nucleus, transcription (genome –> mRNA), translation (mRNA –> precursor proteins), cleavage of precursor proteins, nucleocapsid assembly, budding, maturation.
What determines HIV’s ability to fuse with a cell? What kind of receptor protein must be present?
gp120 (viral envelope glycoprotein) interacts w/CD4 receptor protein on cell, therefore must be CD4+. Common host = Helper T cells. MUST HAVE CORECEPTOR ENGAGEMENT: interaction w/ CCR5 (chemokine receptor superfamily) or CXCR5. Last, gp41 enables fusion w/cell.
Some individuals are resistant to HIV infection. why?
mutation in CCR5 (HIV unable to engage w/host cell).
What components are necessary for HIV replication and from where (host or virus) do they come?
from virus: reverse transcriptase, RNA template, integrase
from host: tRNA primer; RNA polymerase (for proviral genome –> mRNA in nucleus)
Why are mutations frequent with HIV?
viral reverse transcriptase and host cell RNA polymerase lack proofreading capability.
What are the symptoms of acute HIV infection?
fever, enlarged lymph nodes, headache, fatigue, sometimes rash
What happens to CD4+ cells during acute HIV infection?
rapid decline via activation-induced death and HIV destruction
How long does seroconversion typically take in HIV infection? How can HIV be detected before then? What happens to CD4+ cells after seroconversion?
2 months or more; detect w/viral load because antibodies not yet present. After seroconversion (antibody activation) CD4+ cells begin to temporarily recover. seroconversion also corresponds w/decreased viral load.
How is chronic HIV infection diagnosed?
HIV serology (ELISA, western blot). also rapid testing & antibody.
What happens to CD4+ cells during chronic infection?
gradual decline due to activation-induced death, destruction by HIV.
How is AIDS defined?
presence of one of 27 conditions that indicate severe immunodeficiency or CD4+ count <15% total lymphocytes.
What is the time frame for HIV progression to AIDS and death?
appr. 2 months acute infection, followed by 5-10 years chronic infection. AIDS –> death = 2 years.
Standard of treatment for HIV:
HAART (highly active antiretroviral therapy.) 3 drugs w/>2 mechanisms of action.
How do nucleoside reverse transcriptase inhibitors function?
they are nucleoside analogs that cause chain termination of DNA strand = PREVENT INTEGRATION.
How do non-nucleoside reverse transcriptase inhibitors (NNRTI) work?
inhibit reverse transcriptase enzyme by binding near active site and reducing functionality. BLOCK SYNTHESIS OF DNA = BLOCK INTEGRATION.
How do protease inhibitors work?
block HIV protease > prevent production of infectious HIV virions.
How do CCR5 antagonists work?
block virion ability to bind to co-receptor.
How do fusion inhibitors treat HIV?
inhibit formation of gp41 fusion complex.
How do integrase inhibitors treat HIV?
block integrase > no HIV production.
What are the six classes of HIV antiretrovirals?
NRTIs, NNRTIs, Protease inhibitors, CCR5 antagonists, fusion inhibitors, integrase inhibitors
Which three antiretrovirals are used as a first-line treatment?
nRTI, nnRTI, and PI
Basic properties of Poxviruses:
contain dsDNA + protein + lipid. large nucleic acid content. contain DNA dependent RNA polymerase (bc replication in cytoplasm cannot use host’s). no symmetry. TWO ways of infection – enveloped and non-enveloped. ONLY DNA virus that express a gene for RNA polymerase to make mRNA instead of using host’s.
How do poxviruses release virion?
budding out or lysis (non-enveloped and enveloped)
How can poxvirus be detected?
autoradiography of 3H-thymidine inclusion bodies in cytoplasm.
Molluscum contagiosum properties:
Poxvirus; transmitted by intimate cutaneous contact; 2-8 week incubation»_space; pearly white papules
Smallpox properties:
Poxvirus; transmitted via respiratory route > upper RI > primary viremia in lungs/liver/spleen > second viremia in skin. Papules, vesicles, pustules. dried virus in pustule is infectious. LIVE vaccine. ONE serotype. humans only.
smallpox vaccination complications
encephalitis; necrosis at vaccination site (vaccinia necrosum); eczema vaccinatum; generalized vaccinia; myo/pericarditis
Rabies properties
Rhabdovirus: bullet shape; enveloped; helical; (-) RNA; contains RNA-dependent RNA polymerase. d/n require viremia (nerves instead!); transmission via bite
Rabies infection route:
nerve cells: travels up peripheral nerves to CNS, back down to salivary glands
rabies symptoms:
hydrophobia (from painful swallowing); coma; psychosis
how is rabies diagnosed?
histology > Negri bodies (cytoplasmic inclusions) in nerve cells then fluorescent antibody
what type of inclusion bodies are seen in Herpes, Pox and Rabies respectively?
Herpes: nuclear
Pox: cytoplasmic
Rabies: cytoplasmic negri bodies
Rabies treatement/vaccine
KILLED vaccine. long incubation > success treating after exposure (but BEFORE cns symptoms). treat w/passive immunization & vaccine.
