HIV Replication Cycle, Table of Genes
Table 1. The HIV-1 GENOME.
Gene/Protein
Activity
Function
env
Structural
Codes for outer protein coat gp160 (then a protease splits it into gp120 and gp41). Different populations of env exist in the brain as in blood (recall, the V3 loop and other hypervariable regions are part of gp120); PoA 2049 (Amsterdam).
gag
Structural
Encodes internal proteins (p17, p24, p7 and p9: the nucleocapsid core). Makes a 53 kD precursor protein which is chopped up into constituent parts.
pol
Structural
Encodes the HIV core: p7, p9, RNA genome, reverse transcriptase, ribonuclease, integrase, protease.
tat
Positive, Regulatory
Trans-activator of transcription. Can accelerate viral protein production of proviral genome several 1000x. Upregulates rev, nef, itself. 86 amino acid long protein. Uses TAR to transactivate by pulling newly forming RNA transcript through the TAR loop.
nef
Negative and Positive
"Negative Regulation Factor", produces a 27 kD protein. The "negative regulatory element" (NRE) located in the LTR reduces the rate of RNA initiation (prevents proviral DNA from making more HIV proteins). Found in cytoplasm. May also affect cellular genes: with nef around, CD4 expression downregulates. Also neg. regulates tat and rev. Increases in nef suppresses viral replication. Many HIV strains have defective nef. Inhibits the induction of NF- B (PoA 2293) which indicates nef may sustain the latency period.
rev
Pos/Neg
Regulatory
"Regulator of expression." Acts as a genetic switch. Located in nucleus/nucleolus. Multiple functions: prevents RNA expression (element is CRS which is part of the HIV genetic code); the more rev, the more full-length RNA is present and thus the greater amount of expression of env proteins--the less rev, the more of the small, spliced RNA pieces that encode the regulatory genes. Downregulates tat and itself. Seems to activate transport of viral mRNA from nucleus into cytoplasm.
vpr
weak, pos
Transcriptional activator. Moderate stimulation of LTR. Not essential for replication but full function unknown. Recent research suggests vpr expression may be correlated to induction of AIDS.
vpu
Negative?
Encodes "viral protein U" which is antigenic. This gene is not found in HIV-2. If vpu is defective, viruses replicate more quickly. Many strains of HIV-1 are defective in vpu and nef. Not found in virions. Variations in gene result in decreased release of virions. Also suppresses CD4/env interactions in the cell. Synthesized in the membranes of the rough endoplasmic reticulum. Efficient release of budding virions. If vpr removed, virions remain "tethered" to cell. Envelope processing.
vif
Infectivity
Encodes "virion infectivity factor." Increases the infectivity of HIV. Found in cell cytoplasm and outside some. Increases efficiency of cell-to-cell (human-to-human?) transmission. However, vif-deficient HIV still infects in vitro, but with lower kinetics.
tnv/tev
Pos/Neg
A fusion protein resulting from a frameshift reading the mRNA--mixes up tat/env/rev--and apparently has full functional capacity of tat and rev.

Other elements:
TAR: Transactivating response sequence responsive to tat protein. Extends out from LTR.
RRE: Rev-responsive element.
CAR: Cis-acting anti-suppression sequence in RNA; responds to rev protein; overrides CRS.
CRS: Cis-acting repression sequence; prevents expression of messengers except in the presence of a functional CAR sequence and rev protein. The genes that encode regulatory proteins have no CRS sequences.
LTR: Long terminal repeat--the same sequences over and over; found at either end of the HIV genome. There are sequences within this LTR that regulate the initiation of RNA synthesis. They may vary in sequence from cell type to cell type (e.g., lymphocytes vs. macrophages) and regulatory proteins in different cells may have different functions.

Information from, among other sources, Haseltine, WA, Replication and Pathogenesis of the AIDS Virus, JAIDS (1988) 1:217-240. Greene, W.C., The Molecular Biology of Human Immunodeficiency Virus Type I Infection, The New England Journal of Medicine (1991) 324:308-317.
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