2-HIV Flashcards
HIV
general
causes AIDS (acquired immunodef syndrome)
-profound immunosupp so lots of infections, malignancies, wasting/CNS degen
retrovirus
long term latent infectio by integrating genome into host DNA
OR short term cytopathic effects
reverse transcriptase copies viral RNA into DNa to integrate = provirus
types of HIV
HIV 1 and 2 known to infect people in US, 1 more prevalent
-2 is more in west africa
acute HIV syndrome
2-6 weeks after initial infection, stage 1
-resembles infectious mononucleosis so headache, fever, rash, swollen lymph nodes, sore throat
-active virus replication in blood and CSF so lymphoid organs seeded with virus
seroconversion
point where Ab can be detected 6-9 weeks after exposure
-window period when viremic so virus is in blood but serologic tests negative so no Ab
asymptomatic infection
latent phase, stage 2
-HIV nearly undetectable in blood but still replicating in lymphoid tissues
-can be up for 10 years but still seropos
aids related complex
ARC
a subset of AIDS pts with persistent fevers, night sweats, weight loss, chronic diarrhea, inflamm skin, persist generalized lymphadenopathy
maybe oral candidiasis or chronic mucocutaneous herpes
will die quickly without treat
AIDS clinical findings
- recurrent infections, CD4 drops <200
- tumors- kaposi sarcoma or non hodgkins lymphoma
- progressie wasting syndrome, cachexia
- AIDS induced dementia
transmission of HIV
- sexual contact
- inoculation with infected blood
- vertical transmission from mother to child
infection process
general
- virus (gp120) binds CD4
- chemokine receptor bind
- gp41 fusion peptide inserts into T cell
- viral and T cell membranes fuse
- inside cell either enter viral replication or proviral/dormant state
chemokine receptors
HIV uses CCR5 and CXCR4
-R5 viruses = macros and memory T cells
-R4 viruses= T cells
can start early in disease with R5 then transition to R4
cytokines with HIV
- TNF-a and IL-2 induce HIV transcription/replication in T
- IL1/3/6, TNF-a, IFN-y, GM-CSF induce HIV rep in monocytes/macros
in general trigger transcription factors NFkB and SP1
infected monocytes/macros
since not as prone to lysis at T cells may serve as in vivo reservoir to transport thru body
-macros derived cytokines will cause AIDS dementia complex = memory loss
killing T cells
via
1. direct lysis by budding HIV
2. virus prod interfere with protein syn so cell death
3. syncytia form of infected cells with uninfect
4. binding of gp120 to infected and uninfect T cells > Ab resp > ADCC
5. CTL mediated destructino of virus infected cells
immunosuppression
T lymph destruction + destruc of follicular dendritic cell network + gp120 prevents binding class II MHC
why immunity not protective
- HIV integrates into DNA so latent
- error prone reverse transcriptase so mutations to evade Abs and CTLs
- HIV Nef protein downreg class I MHC so CTLs not bind
- seroconversion signals Ab prod but CTL more important after intial infection
causes of death
from infection by protozoan, bacterial, viral opportunistic pathogens
OR
malignancies like kaposi sarcoma or lymphoma
fatal pneumonia from pneumocystis jiroveci most freq COD
obstacles to vaccine develop
- genetic diveristy of HIV strains
- lack of good animal model
- transmission of HIV within cells instead of free viral particles
- viral progression in face of immune resp
HIV resistant indivs
CCR5 variants are seroneg after repeat exposure but can still be infected by R4 strain
also if have potent CTL resp
ELISA
screening tech using HIV antigens cultured in H9 cell line
-antigens absorbed to solid phase and pt serum added then secondary antibody conj to enz
if color change then pos, repeat test, then do western blot to confirm
pros/cons ELISA
-high false pos rate bc cross reacts with Ab to H9 antigens
-reasonable cost
-screen large numbers of samples
-configured to detect viral antigens
western blot
viral antigen sep using SDS PAGE then transfer to membrane incubated with pt serum + antihuman immunoglobulin
-add substrate and see if rxn where pt Ab bound
aka detrmines viral proteins that have Abs
PCR
very sensitive but only detects viral genome DNA integrated so use for neonates
RT-PCR will detect free virus in body fluids so assess viral load in adults
