Table 2.

HIV-1 viral genes and their products, function, and polymorphismsa

Viral GenesGene Products and FunctionComments
gagP55 cleaved by viral protease into four structural proteins: Matrix (p17), capsid (p24), nucleocapsid (p9), and p6Present in all retroviruses
polReverse transcriptase, protease, and integrase enzymesTargets of reverse transcriptase inhibitors and protease inhibitors. Polymorphisms responsible for drug resistance.
envGp160 cleaved by host protease into gp120 and gp41 that are essential for viral cell entry. Gp120 binds with CD4 (HIV receptor) and either CCR5 or CXCR4 (HIV co-receptors). Co-receptor binding is determined by the sequence of V3 variable loop of gp120. The V3 loop is also the principal target for neutralizing antibodies. Gp41 facilitates fusion of viral envelope and cell membrane after binding of gp120 to its receptor and co-receptor; target of fusion inhibitors.CCR5 is expressed in dendritic cells, macrophages, and T-cells; “M-tropic” HIV variants use the CCR5 co-receptor. CXCR4 is expressed mainly in CD4+ T cells; “T-tropic” HIV variants use CXCR4 co-receptor. gp41polymorphism affects the intracellular distribution of Env, its incorporation into virions and viral replication capacity. Alterations in gp41 confer resistance to HIV fusion inhibitors.
tatTransactivator, binds to the transactivation response element located in the long terminal repeat region of HIV RNAPotent transcription factor that enhances HIV genome transcription; possible pathogenic role in HIVAN.
revRegulator of viral expressionFacilitates unspliced genomic HIV-1 mRNA translocation from the nucleus to the cytoplasm.
vpuViral protein UDownregulates CD4 production by inducing its proteolysis, reduces viral cytopathic effect, facilitates the release of new HIV-1 virions from the surface of infected cells; present only in HIV-1.
vprViral protein RTransports pre-integrated HIV genome to the nucleus and induces cell-cycle arrest; possible pathogenic role in HIVAN.
vifViral infectivity factorAffects viral infectivity, counteracts intracellular antiviral factors produced in certain cell types.
nefNegative-regulation factor; likely key pathogenic factor in development of AIDSAugments viral replication and infectivity. Downregulates cell surface CD4 antigen and MHC class I molecules. Downregulates T-cell receptor/CD3 in HIV-2 and simian immunodeficiency virus. This function is protective by maintaining low level of immune activation in infected host and has been lost in HIV-1. Mutations in SH3-binding domain blunt progression to AIDS in transgenic mice. Transgenic mouse models suggest direct pathogenic role in kidney cells.
  • a HIVAN, HIV-associated nephropathy.