HIV Replication and Pathogenesis Flashcards
When, where and who exposed humans to HIV
1902-1921 in Cameroon
Chipanzees
What are the most common methods of transmission of HIV?
Unprotected sex with an infected partner
Sharing needles with infected person
What are the almost eliminated risk factors for the transmission of HIV?
Transmission from infected mother to fetus
Infection from blood products
What is the order of individuals who are infected with HIV?
63%– Gay and Bisexual men
25%– Heterosexuals
8%– Injection drug users
3%– Gay and Bisexual men who also inject drugs
With respect to ethnicity, who is most susceptible to an HIV infection?
African American males–> females
Then hispanic males–> females
Then white males–> females
With respect to age, who are the individuals who are most susceptible to an HIV infection?
young people ages 13-24
Who are the most susceptible to an HIV infection?
young, gay black men
What does the HIV infection first infect in order to spread throughout the body?
lymphoid cells embedded in the vaginal and rectal epithelium—> spread to the lymph nodes and blood
What are the features of HIV?
RNA virus Retroviridae Lentinvirus--slow to cause dz ssRNA, + strand Two copes in each virion (diploid)
What does HIV bind early on in the infection?
HIV binds to CCR5 coreceptor–> macrophages
Non-synctium inducing
What does HIV bind late in the infection?
HIV binds CXCR4 coreceptor –> T cells
synctium inducting
Describe attachment and fusion of HIV…
Viral membrane has transmembrane and surface domains
SU–binds CD4 and chemokine receptors–causing conformational change in TM
Fusion peptide on TM–inserts in target cell and induces virus entry
What determines the susceptibility to HIV infection?
Presence of CCR
What occurs after attachment of the HIV and before reverse transcription of the ssRNA genomes to DNA?
Attachment then membrane fusion
Uncoating occurs and the capsid partially disintegrates
What does HIV use in the cytoplasm to begin reverse transcriptase?
Deoxynucleotides (dNTPs)
RT enzyme–which is error prone
After reverse transcriptase occurs and the ssRNA is now DNA, what is the DNA genome attached to and what is its role?
HIV protein Integrase—> has nuclear localization signal that directs it to the nucleus
What serves as the primer for DNA synthesis from the HIV ssRNA?
tRNA bound to ssRNA is a primer
What is the primary obstacle to eradicating HIV from a person?
HIV provirus integrates into the host chromosome–creating a reservoir of latent virus throughout the body and latency is the primary obstacle to eradicating the HIV
What marks the end of Phase I of HIV replication?
Integration
What marks the start of Phase II of HIV replication
Viral and cellular transcription factors bindig to the promotor in the LTR and recruiting RNA Pol II–> mRNAs transcribed, spliced, and exported to the cytoplasm
HIV mRNAs that are translated on ribosomes form what?
Gag-Pol precursor
Short mRNAs encode what?
the Environment for viral attachment and fusion
Translated in the rough ER
What cleaves the integral membrane proteins used for attachment and fusion?
host proteases–> cleaves into SU + TM domains
Target for therapy
When the Virions are formed from the budding off of the PM are they infectious?
NO–these are immature virions
