Exam 4 - HIV Flashcards
1
Q
HIV classification
A
+ssRNA
- replicate via double-stranded DNA intermediate
- Retroviridae family
- Lentivirus genus
2
Q
HIV was first observed in
A
homosexual young men, previously healthy
3
Q
HIV initially presented as
A
unusual Kaposi’s sarcoma
4
Q
what led to HIV being observed in heterosexuals?
A
- blood transfusions
- hemophiliacs
- injection drug users (shared needles)
5
Q
HIV was discovered by
A
isolating a retrovirus from a lymph node biopsy of an AIDS patient
6
Q
_____________ team was the first to isolate HIV-2
A
Montagnier’s
7
Q
Hunter theory of origin of HIV
A
bushmeat hunting exposed humans to SIVcpz which adapted to become HIV-1
8
Q
Group ___ is the most common HIV-1 subtype (99%)
A
M
9
Q
Polio vaccination campaign did not ______________ which could have _______________
A
always use sterilized syringes; helped initial spread of HIV
10
Q
How did the colonization of French Equatorial Africa help with the spread of HIV?
A
- labor cmaps. unsanitary conditions, starvation
- poor health, weakened immune system
- bushmeat hunting
- unsanitary smallpox vaccinations, sleeping sickness treatment
11
Q
what are the 3 discarded “ideas” on the origin of HIV?
A
- oral polio vaccine (not contaminated with SIVcpz)
- house cat theory (FIV does not affect humans)
- conspiracy theory (HIV present before genetic engineering technology)
12
Q
HIV transmission
A
blood, semen, vaginal fluids, breast milk
13
Q
kissing and oral sex can only transmit HIV if
A
abraisions/lesions are present in the mouth
14
Q
rare modes of HIV transmission
A
- blood transfusions
- organ translplant
- accidental needlestick injuries
- sharing HIV contaminated needles/razors
- premastication
15
Q
HIV is NOT transmitted by
A
- sweat, saliva, tears, mucus
- handshakes, hugs
- surfaces
- insects
16
Q
HIV is an enveloped virus, meaning
A
it is not stable if left out in the air on surfaces
17
Q
timeline for HIV infection in the body
A
- virus crosses mucosal barrier (2-6 hours)
- local propagation of infection on CD4+ T cells (3-6 days)
- systemic dissemination (6-25 days)
18
Q
initial HIV infection is typically in ____________ and _____________ cells
A
macrophages; dendritic cells
19
Q
HIV viral reservoir
A
- latent in infected memory T cells and monocytes
- latency established early in infection (3 days)
20
Q
clinical progression of HIV/AIDS
A
- long disease progression
- hinders and destroys the adaptive immune system
- Opportunistic infections result in death
21
Q
there are ___ stages in HIV-1 infection
A
3
22
Q
HIV replication rate is measured by
A
viral load
23
Q
immunologic damage is measured by
A
CD4 count
24
Q
acute HIV infection
A
- 2-4 weeks
- flulike symptoms, acute retroviral syndrome (ARS)
- CD4 count drops
25
acute HIV infection replicates __________ and establishes ______________________
rapidly; systemic infection
26
seroconversion window
- production of HIV antibodies after infection
- adaptive immune system starts to kick in
27
acute HIV clinical latency
- no/few signs or symptoms
- 8-10 years (w/o ART)
- can detect HIV antibodies
- immune system somewhat controls HIV infection
- HIV replicates at very low levels
- eventually viral load rises and CD4 count declines (immune system loses)
28
systemic infection or AIDS
- immune system is badly damaged
- vulnerable to opportunistic infections, cancers, and co-infections (TB, HCV)
29
AIDS is diagnosed by
- one or more opportunistic illnesses
- CD4 count falls below 200
30
AIDS survival without treatment is _________
~3 years
31
AIDS survival without treatment and dangerous opportunistic illness is ________
~1 year
32
opportunistic infections occur due to
impairment in the immune system
33
opportunistic infections
new infections and reactivation of latent infections (HSV's)
34
what factors affect what opportunistic infections a person is susceptible to?
- exposure to disease
- general health and lifestyle
- socioeconomic factors
- access to diagnostic tests
35
rapid progressors leads to AIDS within ____ years
4
36
intermediate or normal progressors leads to AIDS within _____ years
10-12
37
long-term non-progressors
- asymptomatic for 12+ years
- normal CD4 (>500) without drug treatment
- detectable viral load
38
elite controllers (rare)
- normal CD4 and CD8 T cell counts
- viral load is undetectable (<50)
39
Laboratory diagnosis of HIV is during the _________ period, which is
eclipse; time between when infection is established and when the virus can be detected by a test
40
laboratory diagnosis of HIV
- antibody screening test (blood and saliva)
- antibody and antigen test (blood)
- nucleic acid amplification (viral load)
41
HIV characteristics/structure
+ssRNA, 2 copies
- enveloped, spherical
- conical capsid (cone-shaped)
- polyproteins (Gag, Pol, Env)
- regulatory proteins, accessory proteins
42
HIV replication cycle (proteins involved)
1. Attachment - CD4 receptor (CCR5) and co-receptor
2. Fusion - at cell membrane
3. Uncoating - release of viral genome
4. Reverse Transcription - RNA --> DNA
5. Integration --> provirus - in nucleus, puts viral DNA into host cell genome
6. Tat enhances transcription, Rev exports viral RNAs
7. Assembly - at membrane, budding
8. Maturation - protease cleaves polyproteins
43
how does deletion of 32 ntds in the CCR5 gene provide resistance to HIV?
CCR5 becomes a nonfunctional receptor and prevents HIV binding and fusion
44
2 copies of CCR5Δ32 provides
resistance to HIV-1 infection
45
1 copy of CCR5Δ32 provides
- reduced chance of infection (fewer CCR5 receptors at cell surface)
- delayed progression to AIDS
46
how is Smallpox similar to HIV?
- attacks immune cells (macrophages)
- uses CCR5 to infect
47
__________ can protect from HIV
smallpox
48
goals of ART (antiretroviral treatment)
- restore and preserve immunologic function
- suppress plasma HIV viral load
- prolong life and preserve quality of life
- prevent HIV transmission
49
why can't ART cure HIV infection?
HIV viral reservoir is established early in infection
50
reverse transcription inhibitors
- NRTIs - chain terminators (stops RT)
- NNRTIs - causes conformational change (blocks/inhibits RT)
51
protease inhibitors
inhibits maturation - prevent cleavage of Gag and Pol
- more side effects
52
fusion inhibitor
T20 binds to gp41 and prevents conformational change
- subcutaneous injection
53
entry inhibitor - CCR5 antagonists
- binds to CCR5 receptor --> conf. change
- prevents interaction of CCR5 with gp120 Env protein
- targets CCR5 virus ONLY
54
Integrase inhibitors (INSTIs)
- prevents integration of viral DNA
- binds to divalent metal ions that are cofactors in the integrase active site
- newest class
55
capsid inhibitors
binds capsid protein (CA) subunits
56
why is there drug resistance in ART?
- high mutation rate due to RT - lacks proofreading
- high genetic diversity and fast turnover
57
HAART (highly active antiretroviral therapy)
- 3 drugs to suppress HIV infection
- distinct targets
- more people living with HIV, less dying
58
drug adherence
taking medications when and how its supposed to be taken
59
HIV virologic rebound
HIV RNA level ≥200 after virologic suppression
60
HIV prevention
- abstinence from sex
- pre-exposure prophylaxis (PREP)
- post-exposure prophylaxis (PEP)
- antiretroviral medications
61
why is there no HIV vaccine?
- nobody with HIV has cleared virus naturally
- haven't been able to elicit both T and B cell response
- lack of good animal model
- biology of HIV is challenging
62
Timothy Ray Brown
- first person cured of HIV
- diagnosed with acute myeloid leukemia (opportunistic infection)
- 2 stem cell transplants (donor is also homozygous for CCR5Δ32
- HIV in remission until death
63
most people living with HIV are in ________
Africa
