HIV-1

HIV-1
Name	Human immunodeficiency virus 1
Caption	Schematic of an HIV-1 virion
Taxon	Lentivirus
Order	Ortervirales
Family	Retroviridae
Subfamily	Orthoretrovirinae
Genus	Lentivirus

HIV-1. It is the most common and pathogenic strain of the human immunodeficiency virus, the causative agent of the global AIDS pandemic. First identified in the early 1980s, this retrovirus primarily targets the immune system, specifically CD4+ T cells, leading to progressive immunodeficiency. Its global spread has had profound impacts on public health, driving decades of intensive biomedical research and the development of antiretroviral therapy.

Structure and genome

The virion is approximately 120 nm in diameter and is enveloped by a lipid bilayer derived from the host cell membrane. This envelope is studded with viral glycoprotein complexes, composed of gp120 and gp41, which facilitate entry into host cells. Within the envelope lies a conical capsid made of the viral protein p24, which encases two single-stranded RNA genomes and essential viral enzymes including reverse transcriptase, integrase, and protease. The positive-sense RNA genome is approximately 9.7 kilobases long and encodes nine genes flanked by long terminal repeats, which are critical for regulation and integration.

Replication cycle

The cycle begins with the binding of gp120 to the primary receptor CD4 on the surface of a target cell, such as a helper T cell or macrophage. This binding induces conformational changes that allow interaction with a co-receptor, typically CCR5 or CXCR4, leading to fusion mediated by gp41 and viral entry. Following uncoating, reverse transcriptase catalyzes the synthesis of a double-stranded DNA copy of the viral RNA, which is then transported into the cell nucleus and integrated into the host chromosome by integrase. Host cellular machinery then transcribes the integrated proviral DNA, producing new viral RNA that is translated into polyproteins. The viral protease cleaves these polyproteins into functional components, allowing new virions to assemble at the cell membrane and bud from the host cell.

Transmission and epidemiology

The virus is transmitted through direct exchange of certain bodily fluids, primarily during unprotected sexual intercourse, via contaminated blood products or sharing of injection drug use equipment, and from mother to child during pregnancy, childbirth, or breastfeeding. Since its emergence, Group M of HIV-1 has caused a global pandemic, with major epicenters including Sub-Saharan Africa, Asia, and the Americas. Surveillance and modeling by organizations like the World Health Organization and the Joint United Nations Programme on HIV/AIDS track its spread, which has resulted in tens of millions of infections and deaths worldwide.

Pathogenesis and clinical stages

Following initial infection, the virus replicates extensively in lymphoid tissue, leading to a sharp decline in CD4+ T cell counts and often an acute retroviral syndrome. The immune response, including cytotoxic T lymphocyte activity, partially controls but does not eliminate the infection, leading to a prolonged clinical latency period. During this chronic phase, ongoing viral replication causes a gradual depletion of CD4+ T cells, weakening the immune system. When the CD4+ count falls below a critical threshold, the individual progresses to AIDS, characterized by the onset of opportunistic infections such as Pneumocystis pneumonia and Kaposi's sarcoma, and neurological disorders.

Diagnosis and treatment

Diagnosis is typically achieved through serological tests that detect antibodies to viral proteins, often confirmed by Western blot or nucleic acid tests that measure viral RNA load. The standard treatment is antiretroviral therapy, which combines drugs from different classes such as nucleoside reverse transcriptase inhibitors, protease inhibitors, and integrase strand transfer inhibitors to suppress viral replication. Landmark clinical trials like ACTG 076 proved the efficacy of zidovudine in preventing mother-to-child transmission. While not a cure, modern ART can reduce viral load to undetectable levels, transforming HIV infection into a manageable chronic condition and preventing transmission, a concept known as Undetectable = Untransmittable.

History and origins

The first cases of the disease that would become known as AIDS were reported in 1981 by the Centers for Disease Control and Prevention among previously healthy homosexual men in Los Angeles and New York City. The virus itself was isolated in 1983 by teams led by Luc Montagnier at the Pasteur Institute and, independently, by Robert Gallo at the National Institutes of Health. Phylogenetic analyses indicate that HIV-1 originated from cross-species transmissions of simian immunodeficiency viruses from chimpanzees in central Africa, likely in the early 20th century. The global dissemination of the pandemic Group M strain is linked to mid-20th century urbanization and changes in transportation networks.

Category:Retroviruses Category:HIV/AIDS Category:Infectious diseases