HIV

Human immunodeficiency viruses, or HIVs, are a group of viruses that infect humans.

They belong to the genus Lentivirus, which is a subgroup of retroviruses. Lentiviruses are known for causing long-duration illnesses with long incubation periods. Over time, HIV causes acquired immunodeficiency syndrome, also known as AIDS. This is a condition where the immune system fails progressively. When this happens, the body cannot fight off opportunistic infections or certain cancers. Without medical treatment, the average survival time after infection is estimated to be 9 to 11 years. This duration depends on the specific HIV subtype found in the person.

The way HIV works inside a cell is a complex, multi-step process. First, the virus uses its envelope proteins to attach to target cells. Specifically, the gp120 protein interacts with the CD4 molecule on the cell membrane. The virus also uses chemokine co-receptors to enter the cell. Once attached, the viral envelope fuses with the cell membrane. This fusion releases the viral contents into the host cell. Inside, a viral enzyme called reverse transcriptase converts the single-stranded RNA genome into double-stranded DNA.

Next, an enzyme called integrase carries this viral DNA into the cell nucleus. The enzyme then integrates the viral DNA into the host's own DNA.

Once the viral DNA is integrated, the virus can follow different paths. It may become latent, which means it stays dormant or quiet. In this state, the virus and the host cell can avoid detection by the immune system. This dormancy can last for up to ten years after the initial infection. Alternatively, the integrated DNA can be transcribed to produce new RNA genomes and viral proteins. The cell uses its own resources to package these into new virus particles. These new particles are then released to begin the replication cycle in other cells.

Scientists have identified two primary species of HIV.

The first is HIV-1, which was originally called lymphadenopathy associated virus or LAV. It was also known as human T-lymphotropic virus 3, or HTLV-III. HIV-1 is the most common type globally and is highly virulent. It is more infective than the second type. The second species is HIV-2, which is largely confined to West Africa. HIV-2 has a lower capacity for transmission and is less infective. In 2020, the International Committee on Taxonomy of Viruses gave them new names. They are now classified as Lentivirus humimdef1 for HIV-1 and Lentivirus humimdef2 for HIV-2.

The structure of the HIV virion is incredibly small and detailed. It is roughly spherical with a diameter of about 120 nanometers. This makes its volume about 100,000 times smaller than a red blood cell. The virus is composed of two copies of positive-sense single-stranded RNA. This RNA codes for nine essential genes. These genes are enclosed in an ovoidal capsid made of 2,000 copies of the p24 protein. An outer matrix of p17 protein surrounds this capsid. Finally, a lipid bilayer envelope surrounds the entire particle. This envelope is taken from the membrane of the human host cell.

HIV targets specific cells in the immune system to survive. These include helper T cells, specifically CD4+ T cells, as well as macrophages and dendritic cells. The virus can also infect microglial cells in the central nervous system. Different strains of HIV show different patterns of cell targeting, known as viral tropism. M-tropic strains, or R5 viruses, use the CCR5 co-receptor to enter cells. These can replicate in both macrophages and CD4+ T cells. X4 viruses use the CXCR4 co-receptor instead. Some dual-tropic strains can use both receptors. This ability to target different cells helps the virus spread through the body.

The loss of CD4+ T cells is the main reason the immune system fails. HIV reduces these cell numbers through several different mechanisms. It can cause the death of infected cells through direct viral killing. It can also cause the death of uninfected bystander cells through a process called apoptosis. Some infected cells undergo pyroptosis, which is a form of programmed cell death. Additionally, CD8+ cytotoxic lymphocytes may kill the infected CD4+ T cells. When the number of these vital cells drops below a critical level, cell-mediated immunity is lost. This loss makes the body susceptible to the many infections that characterize AIDS.