HIV

Lore & Background

HIV is a member of the genus Lentivirus, part of the family Retroviridae. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry into a target cell, the viral RNA genome is reverse transcribed into double-stranded DNA by the enzyme reverse transcriptase, then integrated into the cellular DNA by integrase. The virus may become latent, avoiding immune detection for up to ten years after primary infection, during which it causes no symptoms. Alternatively, integrated viral DNA can be transcribed to produce new virus particles. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is more virulent and infective, causing the majority of global infections. HIV-2 is largely confined to West Africa due to its relatively poor capacity for transmission. The viral envelope, derived from the host cell membrane, contains envelope proteins (gp120 and gp41) that allow attachment and fusion with target cells. The envelope protein is a major target for vaccine efforts due to its dense glycosylation, which shields the virus from antibody neutralization.

Reader's Guide

HIV is a significant pathogen because it causes AIDS, a condition that progressively destroys the immune system, leading to susceptibility to opportunistic infections and cancers. Without treatment, average survival time after infection is 9 to 11 years. HIV is primarily a sexually transmitted infection but can also be transmitted via blood, from mother to child during pregnancy, childbirth, or breastfeeding. Research has shown that HIV is not contagious during sexual intercourse without a condom if the HIV-positive partner has a consistently undetectable viral load. The virus infects vital immune cells, including CD4+ T cells, macrophages, and dendritic cells. It reduces CD4+ T cell levels through mechanisms such as pyroptosis, apoptosis, direct viral killing, and killing by cytotoxic lymphocytes. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, leading to AIDS. HIV's ability to integrate into host DNA and remain latent complicates treatment and eradication. The envelope protein's dense glycosylation poses challenges for vaccine development, though recombinant trimeric viral spikes (SOSIP trimers) are promising vaccine candidates. The virus's genetic complexity, with nine genes encoding 19 proteins, allows it to regulate replication, evade immune responses, and cause disease.

Did You Know?

• HIV is present in bodily fluids as both free virus particles and virus within infected immune cells.
• HIV-1 is more virulent and infective than HIV-2, which is largely confined to West Africa.
• The viral envelope protein is one of the most densely glycosylated molecules known, with glycans shielding it from antibody neutralization.
• The virus can remain dormant in the human body for up to ten years after primary infection without causing symptoms.