HIV can complete its replication cycle in the host cell to produce progeny virus, or, like other retroviruses and herpesviruses, establish a latent infection in which the provirus remains quiescent. What determines whether infection of a cell results in latency or a productive infection is unclear, but is thought to be related to the activation state of the cell infected. As we will discuss in the next section, transcription of the provirus following integration is initiated by host transcription factors, which are induced by immunecell activation.
Viral cDNA enters nucleus and is integrated into host DNA Reverse transcriptase copies viral RNA genomes into double-stranded cDNA Viral envelope fuses with cell membrane allowing viral genome to enter the cell Virus particle binds to CD4 and co-receptor on T cell nucleus CD4reverse transcriptase viral RNA genomegp41 gp120 viral cDNA provirus chromosomal DNA cytoplasm co-receptor cell membrane The late proteins Gag, Pol, and Env are translated and assembled into virus particles, which bud from the cell Tat ampliÿes transcription of viral RNA. Rev increases transport of singly spliced or unspliced viral RNA to cytoplasm RNA transcripts are multiply spliced, allowing translation of early genes tat and rev T-cell activation induces low-level transcription of provirus gp160PolGagTatNFB˜Rev
Fig. 13.30 The life cycle of HIV. top row: the virus binds to CD4 using gp120, which is altered by CD4 binding so that it now also binds a chemokine receptor that acts as a co-receptor for viral entry. this binding releases gp41, which causes fusion of the viral envelope with the cell membrane and release of the viral core into the cytoplasm. Once in the cytoplasm, the viral core releases the Rna genome, which is reverse-transcribed into double-stranded cDna using the viral reverse transcriptase. the double-stranded cDna migrates to the nucleus in association with the viral integrase and the Vpr protein and is integrated into the cell genome, becoming a provirus. Bottom row: activation of CD4 t cells induces the expression of the transcription factors nFκB and nFat, which bind to the proviral ltR and initiate transcription of the HiV genome. the first viral transcripts are extensively processed, producing spliced mRnas encoding several regulatory proteins, including tat and Rev. tat both enhances transcription from the provirus and binds to the Rna transcripts, stabilizing them in a form that can be translated. Rev binds the Rna transcripts and transports them to the cytosol. as levels of Rev increase, less extensively spliced and unspliced viral transcripts are transported out of the nucleus. the singly spliced and unspliced transcripts encode the structural proteins of the virus, and unspliced transcripts, which are also the new viral genomes, are packaged with these proteins to form many new virus particles.
Thus, infection of a cell that becomes dormant soon after infection might favor viral latency, whereas infection of activated cells favors productive viral replication. This has important consequences in the case of CD4 T cells, which, unlike macrophages and dendritic cells, are very longlived and can provide a reservoir of latent HIV provirus that can be activated when the T cells are reactivated, even years after initial infection. Because macrophages and dendritic cells in tissues are shortlived cells that do not divide, latency in these