Human Immunodeficiency Virus (HIV) remains a significant global public health concern. The virus attacks the body’s immune system, the natural defense against infections and diseases. Approximately 88 million people have become infected with HIV since the beginning of the epidemic. Untreated HIV infection progressively weakens the immune system, making individuals vulnerable to various illnesses.
The Main Target: CD4+ T Cells
HIV primarily targets and infects CD4+ T cells, a type of white blood cell known as lymphocytes. These cells are components of the adaptive immune system, acting as “helper” cells that coordinate immune responses. CD4+ T cells recognize and respond to foreign invaders, helping the body fight off viruses and bacteria.
These cells are the main target due to the CD4 receptor on their surface. HIV initiates infection by binding its outer envelope glycoprotein, gp120, to this CD4 molecule. This interaction is the first step in the virus gaining entry into the cell. Without the CD4 receptor, HIV cannot effectively attach to and infect the cell.
How HIV Gains Entry
The process of HIV gaining entry into a host cell is a complex mechanism. After the initial binding of the viral gp120 protein to the CD4 receptor on the T cell surface, a conformational change occurs in gp120. This change exposes a binding site for additional host cell proteins known as co-receptors.
The two main co-receptors used by HIV are CCR5 and CXCR4. CCR5 is utilized by most HIV strains in early infection, while CXCR4-using strains emerge later in disease progression. Binding to a co-receptor, along with CD4, triggers further structural changes in the viral envelope protein. This enables the viral and cellular membranes to fuse, allowing the viral contents to enter the host cell’s cytoplasm.
Beyond T Cells: Other Infected Immune Cells
While CD4+ T cells are the primary targets, HIV can also infect other immune cells that express the CD4 receptor and co-receptors. Macrophages play a role in HIV persistence and pathogenesis. These cells can be infected by both CCR5- and CXCR4-tropic HIV strains and may serve as viral reservoirs.
Dendritic cells, which are antigen-presenting cells, can also be infected by HIV. They are among the first cells to encounter HIV during transmission. While their direct infection may be less efficient than T cells, dendritic cells can capture and transfer virions to CD4+ T cells, facilitating viral dissemination within the body. Microglial cells, found in the central nervous system, are another type of macrophage that can be infected by HIV, contributing to neurological complications.
Consequences of Cellular Infection
The infection of CD4+ T cells by HIV leads to their progressive depletion and dysfunction. This occurs through various mechanisms, including direct viral killing, programmed cell death (apoptosis) of infected and uninfected bystander cells, and the immune system’s attempt to clear infected cells. The rapid turnover of these cells, combined with impaired production of new T cells, compromises the immune system’s ability to fight off infections.
This compromised immune system results in immunodeficiency, leaving the body vulnerable to opportunistic infections and certain cancers that a healthy immune system would normally control. For instance, individuals may develop severe bacterial infections, tuberculosis, or specific cancers like Kaposi’s sarcoma. Infection of macrophages and microglial cells can also contribute to widespread inflammation and specific organ dysfunction, such as neurological problems.