human immunodeficiency virus

human immunodeficiency virus. It is a lentivirus, a subgroup of retroviruses, that targets the human immune system, specifically CD4+ T cells, macrophages, and dendritic cells. Infection leads to a progressive depletion of these critical immune cells, resulting in acquired immunodeficiency syndrome if left untreated. The two major types, HIV-1 and HIV-2, originated from cross-species transmissions of simian immunodeficiency viruses from non-human primates to humans.

Overview

The discovery of the virus was first reported in 1983 by teams led by Luc Montagnier at the Pasteur Institute in France and later by Robert Gallo at the National Institutes of Health in the United States. The ensuing global pandemic has had a profound impact on global public health, leading to the establishment of major international bodies like the Joint United Nations Programme on HIV/AIDS. Infection progresses through stages, from acute infection to clinical latency, and ultimately to AIDS, characterized by opportunistic infections and cancers such as Kaposi's sarcoma.

Structure and genome

The virion is roughly spherical, approximately 120 nm in diameter, and is enveloped by a lipid bilayer derived from the host cell membrane. This envelope is studded with glycoprotein complexes, primarily composed of gp120 and gp41, which are critical for attachment and entry into host cells. Inside the envelope lies the viral capsid, a conical core that houses two identical strands of RNA and vital enzymes including reverse transcriptase, integrase, and protease. The genome is approximately 9.7 kilobases long and encodes nine genes, including gag, pol, and env, which are flanked by long terminal repeats.

Replication cycle

The cycle begins when the viral gp120 binds to the CD4 receptor and a co-receptor, typically CCR5 or CXCR4, on the surface of a host cell. This triggers fusion of the viral and cellular membranes, mediated by gp41, allowing the viral core to enter the cytoplasm. Reverse transcriptase then catalyzes the synthesis of a DNA copy from the viral RNA template, forming a proviral DNA complex. This complex is transported into the cell nucleus and integrated into the host chromosome by the viral integrase. Host cellular machinery, such as RNA polymerase II, transcribes the integrated proviral DNA into new viral mRNA, which is translated into polyproteins. The viral protease subsequently cleaves these polyproteins into functional components, and new virions assemble and bud from the host cell membrane, acquiring their envelope.

Transmission

The virus is transmitted through direct exchange of certain bodily fluids. The most common routes include unprotected sexual intercourse, sharing contaminated hypodermic needles or syringes, and from mother to child during pregnancy, childbirth, or breastfeeding. Historically, transmission also occurred through contaminated blood transfusions and blood products before the implementation of widespread screening, notably affecting groups such as hemophilia patients. Notable cases that heightened public awareness include that of Ryan White in the United States and the tainted blood scandal in the United Kingdom.

Diagnosis and treatment

Diagnosis is primarily achieved through serological tests that detect antibodies or antigens, such as the p24 antigen, with confirmatory testing via Western blot or nucleic acid tests. The standard treatment is antiretroviral therapy, which typically combines drugs from several classes, including nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors, and entry inhibitors. Landmark trials like ACTG 076 demonstrated the efficacy of zidovudine in preventing mother-to-child transmission. While not a cure, modern ART can suppress viral load to undetectable levels, transforming the infection into a manageable chronic condition and preventing transmission, a concept known as Undetectable = Untransmittable.

Epidemiology and history

The pandemic is believed to have originated from zoonotic transmissions of SIV from chimpanzees and sooty mangabeys in Central Africa in the early 20th century. The modern pandemic was first recognized in 1981 when the Centers for Disease Control and Prevention reported clusters of Pneumocystis pneumonia among previously healthy homosexual men in Los Angeles and New York City. The disease spread rapidly globally, with severe early outbreaks in regions like Sub-Saharan Africa, Haiti, and Thailand. The global response has been spearheaded by organizations like the World Health Organization and initiatives such as the President's Emergency Plan for AIDS Relief. Despite advances, significant epidemics persist in countries like South Africa, Nigeria, and Mozambique. Category:Retroviruses Category:HIV/AIDS