Micro: Retroviruses

Question 1

what is a retrovirus

Answer 1

retro- for reverse
RNA genome -> DNA -> RNA
blood borne pathogens

Question 2

what are the human retroviruses

Answer 2

HIV (human immunodeficiency virus) - HIV1 and HIV2
Human T-cell Leukemia Virus - AKA T-lymphotropic virus
- HTLV1 and HTLV2

Question 3

what is the US epidemiology of HIV

Answer 3

most clinically relevant of the retroviruses
bigger problem in other countries than US
roughly 1.2 million pts living with HIV in the US
highest in AA pts
most new diagnoses from male-to-male sexual contact, 2nd heterosexual contact, 3rd IV drug use

Question 4

what is the pathophyisiology of HIV

Answer 4

viral structure - enveloped virus
viral entry: HIV infects T-lymphocytes (WBC), entry requires co-receptors, after binding to the co-receptor, GP41 is exposed -> membrane fusion
Viral replication: reverse transcriptase, integrase, host transcription and translation process are used
Viral Assembly

Question 5

what is a viral life cycle

Answer 5

1. binding
2. fusion
3. penetration
4. reverse transcription
5. transport
6. integration
7. transcription
8. translation
9. cleavage
10. assembly
11. budding and maturation

Question 6

what is the purpose of the lipid bilayer

Answer 6

helps to evade the immune system, sensitive to UV, heat, compounds, etc.

Question 7

what receptors are required for viral entry

Answer 7

co-receptors
CCR5 or CXCR4
bind envelope protein to GP120

Question 8

what is reverse transcriptase

Answer 8

converts viral RNA into DNA
contains DNA polymerase and ribonuclease (RNase)
DOESN’T contain exonuclease (proof-reading)
highly error prone (mutations)

Question 9

what is integrase

Answer 9

joins viral and host DNA
can penetrate a non-dividing nucleus (need activation)
occurs at random sites
uses host repair mechanisms
nearly impossible to remove
viral replication now also aided by infected cell replication

Question 10

what are the host transcription and translation processes used

Answer 10

DNA polymerase
RNA polymerase
when occurring -> active infection
latent infection = no viral RNA production

Question 11

what is part of viral assembly

Answer 11

HIV polyproteins contain all necessary viral components in one structure
polyproteins clump together in the cytoplasm - > stimulates budding
HIV polyproteins combine to form an immature viral particle

Question 12

what do HIV polyproteins combine to form

Answer 12

an immature viral particle

Question 13

what is protease

Answer 13

protease cleaves full length proteins into usable proteins -> viral maturation

Question 14

what is protein cleavage

Answer 14

infectious

Question 15

what are the treatment targets

Answer 15

CCR5 coreceptor antagonist (maraviroc)
Fusion inhibitor (enfuvirtide)
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
Nucleoside and nucleotide reverse-transcriptase inhibitors (NRTIs)
Integrase stand-transfer inhibitors (INSTIs)
Protease inhibitors

Question 16

What is Stage 1 HIV

Answer 16

acute HIV infection
aka acute retroviral syndrome
acute viral illness following initial infection with HIV (flu-like)
days to weeks after initial infection
highly infectious during this period

Question 17

what is the pathophysiology of acute HIV infection

Answer 17

rapid increase in viral load - immune system activation (antibody production)
CD8 cells (cytotoxic T cells) destroy HIV infected cells
Rapid destruction and drop in CD4 counts

Question 18

what is stage 2 HIV

Answer 18

chronic HIV infection
Aka latent or asymptomatic HIV infection
months to years after initial infection
not all viral particles destroyed by initial CD8 attack
some HIV infected cells remain - low level replication
decreased rates of CD4 destruction
overtime, HIV viral load and CD4 counts decrease

Question 19

what is stage 3 HIV

Answer 19

advanced HIV disease
aka acquired immunodeficiency syndrome (AIDS)
high viral loads and significantly low CD4 counts
highly infectious
high mortality rate (survival ~3 years)

Question 20

what are the CD4 count for the dx of stage 3 HIV

Answer 20

CD4 count < 200 or presence of certain opportunistic infection(s)/cancers
occurs more frequently or are more severe in pts with compromised immune systems