L22- HIV Flashcards
HIV: family, subfamily, genus
Family- retroviridae
Subfamily- orthoretroviridae
Genus- lentivirus
list the important properties of the Lentivirus genus
- infects immune cells
- provirus permanently in infected cells (latent infections via reverse transcriptase)
- causes slow, progressive, chronic disease
-non-oncogenic viruses
HIV: group, genome make-up (include ORF), virus / core shape and structure
Group VI- (+)ssRNA, 2 copies
-9 open reading frames => ~15 proteins
- enveloped, spherical shape
- inverted cone or bullet shaped core with genome
(1) is the term for when HIV genome is integrated with host genome
viral mRNA codes for (2) in a (3) structure
1- provirus
2/3- non-structural (core) and structural (envelope, capsid) proteins each in a polyprotein form –> cleaved into proteins as final step of maturation
HIV main external Ags (include brief functions):
- (1) surface
- (2) transmembrane
- (3) precursor to (1)/(2)
1- gp120- binding to CD4 receptor
2- gp41- fusion and entry (possibly binding to co-receptor)
3- gp160 –> cleaved into gp120, gp41
list the 3 main genes found in all retroviruses and include what they code for generally
gag (group specific Ag): core, matrix, capsid proteins (p17, p24)
pol (polymerase)- reverse transcriptase, protease, integrase
env (envelope)- transmembrane glycoproteins (gp120, gp41)
Note- HIV has the most accessory genes of all retroviruses
-LTRs- long terminal repeats for gene expression once integrated
list the modes of HIV transmission (include infected body fluids)
- unprotected sex (vaginal, oral, anal)
- shared needles/syringes
- vertical transmission
Body fluids: blood, semen, vaginal fluids, pre-seminal fluid, rectal fluids, breast milk
-contact with mucosa, damaged tissue, or blood-to-blood
HIV:
- increases the risk of getting (1) infections, note before AIDS
- (2) may decrease heterosexual transmission of HIV
- (3) discuss survival of HIV in environment
1- other STIs
2- circumcision
3- doesn’t survive outside host long
HIV uses (1) to bind to (2), the main receptor. (3) is the initial co-receptor found on (4). (5) is the secondary co-receptor found on (6).
1- gp120
2- CD4 receptors
3/4- (m-tropism, early and less aggressive phase) CCR5: macrophages, dendritic cells, CD4 T cells (APCs)
5/6- (t-tropism, late and more aggressive phase) CXCR4: CD4 T cells
what is unique property of reverse transcriptase in terms of genome replication
- viral (+)ssRNA –> dsDNA
- *poor proofreader –> random errors
-uses host nucleotides
(1) will use viral dsDNA to create provirus
(2) will cleave polyprotein translated from viral mRNA to mature viral proteins; (3) is the key sign that a HIV virus has matured
1- integrase
2- protease
3- change of core shape –> bullet shaped (inverted cone shape)
(1) is the key receptor in the brain that HIV attaches to on (2) cells, resulting in formation of (3)
1- CCR3
2- microglial cells
3- brain nodules
initially HIV viruses enter the body and bind to (1) cells, leading to (2) progression before development of acute viremia
- macrophages: internalized –> goes to LNs
- dendritic cells: accumulates on surface –> goes to LNs –> CD4 T cells infected
what parameters lead to AIDS diagnosis
1) T cells count <200
2) AIDS defining opportunistic infections
describe the two methods HIV uses to avoid Ab detection + the method to shied HIV from the immune system in general
1) gp120 antigenic drift (random errors via reverse transcriptase)
2) syncytia formation –> direct cell-to-cell spread (as opposed to cell lysis)
-viral latency / provirus in T cells and APCs shield virus from immune system
what is the function of HIV infecting dendritic cells, macrophages, and Th cells (CD-4) // APCs
loss of activators and controllers of immune system
(T/F) antiretroviral drugs are able to eliminate latent HIV
F- no ARV has this function
describe the cytopathic effects or cellular changes (often seen with in the brain)
HIV encephalopathy:
- syncytial fusion of macrophages, microglial cells (to bypass immune system)
- multinucleated giant cells (as a result of this fusion)
list the stages of HIV infection + timeline
1) Acute HIV (acute retrovial syndrome), 2-4wks post-exposure
2) Chronic HIV, asymptomatic latency, years
3) AIDS, T cell count <200 and or AIDS defining opportunistic infections
Acute HIV:
- (1) timeline
- (2) prevalence
- (3) symptoms
- (4) pathogenesis
1- 2-4wks post-exposure
2- 50-60% of Pts (non-specific / flu-like Sxs)
3- fever, HA, rash, lymphadenopathy, **oral ulcers (+ penis, anus)
4- rapid multiplication of virus + disseminated destruction of CD4 T cells –> high viral levels in blood, high risk of transmission
Chronic HIV:
- (1) main occurring process
- (2) possible signs and symptoms
1- progressive decline of CD4 T cells
2- generalized lymphadenopathy + greater frequency and severity of some infections (thrush, VZV/shingles, cervical dysplasia)
describe the distribution and timeline of HIV infected patients developing AIDS (w/o treatment)
80%, typical progression: 7-10 yrs
5-10%, rapid progression: <2yrs
10-15%, non-progression
describe the timeline of viral copies in plasma and T cell count in HIV infections
Acute HIV: massive spike in HIV viral numbers + large decline in T cell count
(viral numbers sharply dec, T cell count bounces back, but not to as high numbers)
Chronic HIV: gradual T cell count decline, gradual viral number inc
AIDS: T cell count <200 –> massive inc in viral numbers
HIV detection:
- (1) is the initial sign of HIV in serum, include timeline
- (2) is the general sign of HIV in serum, include timeline
- (3) describe window period
1- p24 Ag: present after 10-12 days, lasts for 2-3 months (afterwards no free Ag –> all is bound // will not inc until T cell count <200)
2- anti-HIV Ab (gp120): not detectable for first 1-2 months
3- first 1-2 mos, no detectable anti-HIV Ab
HIV testing:
- (1) recommendation for all people
- (2) recommendation for high-risk individuals
- (3) recommendation for pregnant patients
1- once in lifetime for everyone 13-64 y/o
2- annually (all STDs)
3- 1st trimester (+ 3rd for high risk Pts)
describe the pre-4th generation HIV testing, including timeline (hint- 3 tests)
1) HIV RNA, 11-12 days post-infection
2) p24 Ag, 14-15 days post-infection
3) ELISA, HIV Abs, 3-8wks post-infection (median ~25 days)
describe the HIV Dx algorithm with 4th generation HIV testing
1) 4th Gen. ELISA: detects p24 Ag and anti-HIV Ab (gp120)
- very high sensitivity/specificty
2) (if positive) HIV1/HIV2 differentiation testing –> HIV1, HIV2 or indeterminant
3) (if inderterminant) HIV1 NAT testing –> (+) HIV1 or (-) HIV2
(1) is the main test for monitoring HIV as it is suggestive of (2). (3) levels are considered undetectable and is the goal of anti-retroviral therapy.
1- viral load (NOT T cell count - too expensive)
2- severity of infection, disease progression –> monitor in therapy
3- <50 copies/mL
list the other testing that is usually completed after an initial HIV diagnosis is made
- test for all other STIs + annual testing: syphilis serology, NAATs for gonorrhea, chlamydia if necessary
- test for HepB, HepC (90% chance of infection if IV drug user with HIV)
- test for Tb
discuss the use of PrEP in terms of HIV
Pre-exposure prophylaxis: \+very high efficacy \+used for HIV neg. Pts at high risk: -high risk and no regular condom use -HIV+ partner -IV drug users sharing injection equipment
