HIV Virus Research

About Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is an enveloped retrovirus in the genus Lentivirus, subfamily Orthoretrovirinae, and family Retroviridae. HIV infects cells that express CD4, particularly CD4-positive T lymphocytes, and uses the chemokine receptors CCR5 or CXCR4 as major entry coreceptors. Progressive loss and dysfunction of CD4 T cells can lead to acquired immunodeficiency syndrome (AIDS) if infection is not effectively treated. Two major human immunodeficiency viruses are recognized: HIV-1 and HIV-2. HIV-1 is responsible for the large majority of infections worldwide and is divided into several phylogenetic groups, including groups M, N, O, and P. Group M contains the principal subtypes and circulating recombinant forms. HIV-2 is genetically related to simian immunodeficiency viruses of sooty mangabeys and is concentrated mainly in West Africa, although infections occur in other regions. Mature HIV-1 particles are approximately 100–120 nm in diameter and contain a host-derived lipid envelope bearing trimeric Env spikes. Each spike is composed of surface glycoprotein gp120 and transmembrane glycoprotein gp41. Beneath the envelope lies the matrix protein MA (p17), while the characteristic conical core is formed mainly by capsid protein CA (p24).

HIV-1 virion structure and genome organization.

The mature capsid encloses two copies of the positive-sense single-stranded RNA genome, nucleocapsid proteins, and essential viral enzymes, including reverse transcriptase, integrase, and protease. Following entry and uncoating, reverse transcriptase converts the viral RNA genome into double-stranded DNA. Integrase then inserts this DNA into a host chromosome, producing a provirus that serves as the template for viral RNA and protein synthesis.

HIV gene expression depends on extensive alternative splicing and the regulatory proteins Tat and Rev. Newly synthesized genomic RNA and viral proteins assemble at the plasma membrane, where immature particles bud from the cell. Viral protease subsequently cleaves Gag and Gag-Pol polyproteins, reorganizing the particle into the mature infectious virion.

Combination antiretroviral therapy suppresses HIV replication by targeting multiple stages of the viral life cycle, including entry, reverse transcription, integration, proteolytic maturation, and capsid function. HIV proteins and genetic variants remain central to studies of viral entry, neutralizing antibodies, immune escape, drug resistance, latency, vaccine development, and reservoir biology.

The HIV-1 RNA genome is approximately 9.3 kb per RNA copy. After reverse transcription and integration, the provirus is flanked by 5′ and 3′ long terminal repeats (LTRs). The principal coding regions include the structural genes gag, pro, pol, and env; the regulatory genes tat and rev; and the accessory genes vif, vpr, vpu, and nef. HIV-2 encodes Vpx rather than Vpu.

Gag is processed into the principal structural proteins MA, CA, NC, and p6. The Gag-Pol polyprotein is produced through ribosomal frameshifting and provides protease, reverse transcriptase, RNase H, and integrase. Env is synthesized as gp160 and cleaved by a cellular protease into gp120 and gp41. Regulatory and accessory proteins control transcription, RNA export, particle release, immune evasion, and resistance to host restriction factors.