HIV/Rabies/PoxViruses

Question 1

What is the structure of HIV?

Answer 1

enveloped retrovirus (2xidentical +RNA) in the lentivirus family. contains reverse transcriptase, integrate & protease.

Question 2

What is the general replication strategy of HIV?

Answer 2

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.

Question 3

What determines HIV’s ability to fuse with a cell? What kind of receptor protein must be present?

Answer 3

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.

Question 4

Some individuals are resistant to HIV infection. why?

Answer 4

mutation in CCR5 (HIV unable to engage w/host cell).

Question 5

What components are necessary for HIV replication and from where (host or virus) do they come?

Answer 5

from virus: reverse transcriptase, RNA template, integrase

from host: tRNA primer; RNA polymerase (for proviral genome –> mRNA in nucleus)

Question 6

Why are mutations frequent with HIV?

Answer 6

viral reverse transcriptase and host cell RNA polymerase lack proofreading capability.

Question 7

What are the symptoms of acute HIV infection?

Answer 7

fever, enlarged lymph nodes, headache, fatigue, sometimes rash

Question 8

What happens to CD4+ cells during acute HIV infection?

Answer 8

rapid decline via activation-induced death and HIV destruction

Question 9

How long does seroconversion typically take in HIV infection? How can HIV be detected before then? What happens to CD4+ cells after seroconversion?

Answer 9

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.

Question 10

How is chronic HIV infection diagnosed?

Answer 10

HIV serology (ELISA, western blot). also rapid testing & antibody.

Question 11

What happens to CD4+ cells during chronic infection?

Answer 11

gradual decline due to activation-induced death, destruction by HIV.

Question 12

How is AIDS defined?

Answer 12

presence of one of 27 conditions that indicate severe immunodeficiency or CD4+ count <15% total lymphocytes.

Question 13

What is the time frame for HIV progression to AIDS and death?

Answer 13

appr. 2 months acute infection, followed by 5-10 years chronic infection. AIDS –> death = 2 years.

Question 14

Standard of treatment for HIV:

Answer 14

HAART (highly active antiretroviral therapy.) 3 drugs w/>2 mechanisms of action.

Question 15

How do nucleoside reverse transcriptase inhibitors function?

Answer 15

they are nucleoside analogs that cause chain termination of DNA strand = PREVENT INTEGRATION.

Question 16

How do non-nucleoside reverse transcriptase inhibitors (NNRTI) work?

Answer 16

inhibit reverse transcriptase enzyme by binding near active site and reducing functionality. BLOCK SYNTHESIS OF DNA = BLOCK INTEGRATION.

Question 17

How do protease inhibitors work?

Answer 17

block HIV protease > prevent production of infectious HIV virions.

Question 18

How do CCR5 antagonists work?

Answer 18

block virion ability to bind to co-receptor.

Question 19

How do fusion inhibitors treat HIV?

Answer 19

inhibit formation of gp41 fusion complex.

Question 20

How do integrase inhibitors treat HIV?

Answer 20

block integrase > no HIV production.

Question 21

What are the six classes of HIV antiretrovirals?

Answer 21

NRTIs, NNRTIs, Protease inhibitors, CCR5 antagonists, fusion inhibitors, integrase inhibitors

Question 22

Which three antiretrovirals are used as a first-line treatment?

Answer 22

nRTI, nnRTI, and PI

Question 23

Basic properties of Poxviruses:

Answer 23

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.

Question 24

How do poxviruses release virion?

Answer 24

budding out or lysis (non-enveloped and enveloped)

Question 25

How can poxvirus be detected?

Answer 25

autoradiography of 3H-thymidine inclusion bodies in cytoplasm.

Question 26

Molluscum contagiosum properties:

Answer 26

Poxvirus; transmitted by intimate cutaneous contact; 2-8 week incubation&raquo_space; pearly white papules

Question 27

Smallpox properties:

Answer 27

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.

Question 28

smallpox vaccination complications

Answer 28

encephalitis; necrosis at vaccination site (vaccinia necrosum); eczema vaccinatum; generalized vaccinia; myo/pericarditis

Question 29

Rabies properties

Answer 29

Rhabdovirus: bullet shape; enveloped; helical; (-) RNA; contains RNA-dependent RNA polymerase. d/n require viremia (nerves instead!); transmission via bite

Question 30

Rabies infection route:

Answer 30

nerve cells: travels up peripheral nerves to CNS, back down to salivary glands

Question 31

rabies symptoms:

Answer 31

hydrophobia (from painful swallowing); coma; psychosis

Question 32

how is rabies diagnosed?

Answer 32

histology > Negri bodies (cytoplasmic inclusions) in nerve cells then fluorescent antibody

Question 33

what type of inclusion bodies are seen in Herpes, Pox and Rabies respectively?

Answer 33

Herpes: nuclear
Pox: cytoplasmic
Rabies: cytoplasmic negri bodies

Question 34

Rabies treatement/vaccine

Answer 34

KILLED vaccine. long incubation > success treating after exposure (but BEFORE cns symptoms). treat w/passive immunization & vaccine.