sexually transmitted viral infections Flashcards
(36 cards)
for surveillance purposes, what is AIDS defined as
- HIV infected individual with “indicator infections” or CD4<200 microliters
structure of HIV
- has a genome with pol gene that encodes the reverse transcripase
- capsular protein called p24
- matrix protein p17
- surface protein with a bridge with gp41 and pedestal gp120
type of virus -HIV family rna/dna? enveloped/not -types
retroviridae virus family
ssRNA
enveloped
2 types HIV1 and 2- one is the most prevalent but 2 is more mild
pathogenesis of HIV
1) attach and fuse with the plasma membrane
2) enters the nucleus and integrates into the host genome and is transcribed
3) leave the cell via budding
4) protein cleavage
step one of HIV pathogenesis in greater detail: how does HIV bind CD4 cells
- uses gp120 to bind CD4
- CD4 found on T lymphocytes, macrophages, and monocytes
- conformational change in gp120 allows it to bind it’s coreceptors CCR5 and CXCR4- which one depends on its tropism
R5 tropic HIV
- uses CCR5 as a coreceptor
- almost always transmitted from person to person and predominant EARLY in disease
- efficiently infects monocytes/macrophages and microglia
X4 tropic HIV
- use CXCR4 as coreceptor
- LATER stages
- 40% of pt transition from CCR5 to CXCR4 during the course of their disease
- associated with rapid progression of the disease
what genetic mutations can be protective against HIV
- some people have a deletion in the region of the CCR5 gene that affects its binding to gp120
A) heterozygous deletion leads to longer asymptomatic period before onset of AIDS
b) homozygous deletion = no infection with Rd-tropic viruses (but still susceptible to CXCR4)
what mediates the fusion of the HIV and cell
-GP41
what occurs after the virus enters the cell? what’s important to note about it’s error rate
- when the virus enters the cell, it engages in reverse transcription to create a dsDNA from the RNA HIV genome
- error rate is high so it allows the virus to change often making it a difficult target
after the dsDNA copy of the genome is created it moves into the nucleus. what occurs then?
- dsDNA copy is incorporated into the host DNA via VIRAL INTEGRASE
- viral DNA integrated into the host genome is called PROVIRUS
- transcribed and replicated like a cellular gene and will remain in the cell as long as it survives
provirus
-the part of the dsDNA that is integrated into the host genome
how do HIV virions exit the cell?
- they do it via budding at lipid rafts (viral protein envelope)
how does the HIV virion mature
uses VIRAL PROTEASE to cleave gag and gag-pol viral polyproteins in a process called virion maturation-essential for infectivity
what’s important to note about transmission of HIV
- more efficient between male to female vs female to male
- most common route worldwide is heterosexual transmission
- genital lesion-causing STDs make pt more likely to transmit
what is the overall transmission risk of a mother giving HIV to child
25%
- before 23-30%
- 50-65% AT BIRTH
- 12-20% after birth via nursing
how likely are you to get HIV via needle stick? mucus membrane
- 0.3%
- 0.09%
how does the antigen and antibodies of and to HIV change over time? how doe CD4 cell counts change? what sort of symptoms do you see throughout the progression of the disease
- antigen (p24) levels are high acutely however, antibodies are made and antigen levels begin to drop as antibodies rise
- CD 4 cells steadily decline
- start with chronic lymphadenopathy and progress to immune dysfunction and then skin and mucous membrane immune defects and finally systemic immune deficiency
what symptoms are associated with acute HIV syndrome
- mononucleosis-like syndrome
- 3-6 weeks post exposure
- rash
- may not have detectible levels of anti-HIV antibodies at this time
during the chronic infection stage of HIV, what can we expect to see?
- low level viremia due to viral replication
- HIV escape immune system due to antigenic drift of gp120 -result of mistake-prone reverse transcriptase
- inactivation of key immune responses
- can uses cell-to-cell fusion to move to different cells without moving extracellularly and activating antibodies
- pt often asymptomatic
- median time untreated 10 yrs
how does HIV reduce CD4 count? what is the ultimate consequence of decreasing CD4 count?
- causes budding of CD4 cells to make the membrane weak and unable to sustain
- interferes with cellular processes
- reduced ability to fight infection
what are some infections that are associated with HIV?
1) oral hairy leukoplakia-Epstein virus
2) pneumonia- pneumocystis carinii and mycobacterium tuberculosis
3) thrush- candida albicans (yeast infection of mouth)
4) CMV retinitis-cytomegalovirus
5) neoplasms- kaposi’s sarcoma (HHV8)-skin lesions/B cell lymphomas
6) Diarrhea
what can we detect pretty early on to diagnose HIV? later?
-HIV RNA and HIV-1 p24 antigen
and then
HIV antibody
according to the algorithm, what do you test for first? if that is positive, what do you test for? if that is negative, what can that be?
- test for presence of antigen/antibody combo via slide containing anti-p24 antibody and viral antigen (tests for HIV1 and 2 antibodies and HIV p24 antigen)
- test for specific antibody to HIV1 and 2.
- if both negative, test for nucleic acids (looks for HIV RNA)- if negative then original was a false positive, if positive then pt is in acute HIV infection
