HIV-1 gag-pol precursor (p160) contains the necessary proteins for
viral replication; protease, RNase, reverse transcriptase, and
integrase. Naturally, the Gag-pol precursor is generated from a
ribosomal frameshift to the pol
reading frame 5% of the
time. During viral maturation, the virally encoded protease cleaves
the Pol polypeptide away from Gag and further digests it to
separate the protease (p10), reverse transcriptase (RT; p50), RNase
H (p15), and integrase (p31). However, cleavage is not always
efficient and a portion of RT may remain attached to RNase H.
Gag-Pol may regulate its own translation, by the binding genomic
RNA in the 5' untranslated region. At low concentrations, the
Gag-Pol polyprotein appears to promote translation, whereas at high
concentrations, the polyprotein encapsidates genomic RNA, thus
turning off translation.
Protease (Pro) is an aspartyl protease that acts as a dimer. It
cleaves viral polyproteins (Gag-Pol, Pol, etc) to yield mature
viral proteins during maturation. Pro is most active between
shortly before and shortly after budding. It targets host proteins
EIF4GI and PABP1 involved in capped cellular mRNA translation to
maximize viral gene expression. It also mediates the cleavage of
CARD8, thus activating CARD8 inflammasome, leading to clearance of
latent HIV-1 in CD4+ T-cells after viral reactivation.
Reverse transcriptase (RT) is a DNA polymerase, which synthesizes
double stranded DNA from the single-stranded genomic RNA. RT can
act on both RNA and DNA templates.
Ribonuclease H (RNase) cleaves the RNA strand (genomic RNA strand)
of RNA-DNA heteroduplexes formed after the initial synthesis of DNA
by RT, leaving single-stranded DNA ready for complementary strand
synthesis. Two polypurine tracts are left by RNase H to serve as
templates for DNA synthesis by RT. After DNA synthesis is
initiated, RNase H removes the polyurine tracts.
Integrase (In) catalyzes the integration of viral DNA (provirus) in
the host genome. First, an exonuclease activity trims two
nucleotides from each 3' end of the linear viral DNA duplex. Then,
a double-stranded endonuclease activity cleaves the host DNA at the
integration site. Finally, a ligase activity generates a single
covalent linkage at each end of the proviral DNA.
For information on the Gag polyprotein, kindly refer to BCH record