The Mechanism of HIV: How the Virus Infects and Replicates

Human Immunodeficiency Virus, or HIV, is a retrovirus that targets and weakens the body’s immune system. Its method of infection involves taking over specific immune cells to create copies of itself, a process that gradually damages the body’s ability to defend against other illnesses. Understanding the mechanisms of this virus is fundamental to comprehending its impact on human health and the strategies used to combat it. This virus represents a significant global health challenge.

The Virus and Its Target Cell

The Human Immunodeficiency Virus particle, known as a virion, is a spherical structure. Its outermost layer is a lipid envelope, taken from a previously infected host cell. Embedded within this envelope are proteins, gp120 and gp41, which act as keys to enter a target cell. Beneath the envelope lies a protein shell called a capsid, which contains the virus’s genetic blueprint—two identical strands of single-stranded RNA—and several enzymes necessary for its replication, including reverse transcriptase, integrase, and protease.

The virus’s primary target is a specific type of white blood cell called the CD4+ T-helper cell. These cells are a component of the adaptive immune system, responsible for coordinating the body’s response to pathogens. The virus’s surface protein, gp120, is specifically shaped to bind to the CD4 protein receptor on the surface of these T-helper cells, which is the first step in the infectious process.

The HIV Replication Cycle

The HIV life cycle begins with binding and fusion, where the gp120 protein on the virion’s surface attaches to a cell’s CD4 receptor. This binding triggers a change in gp120, allowing it to also bind to a co-receptor (either CCR5 or CXCR4). This dual-receptor interaction enables the gp41 protein to fuse the viral and cell membranes, allowing the viral capsid to enter the cytoplasm.

Once inside, the reverse transcriptase enzyme converts the viral RNA into a double-stranded DNA copy of the virus’s genetic code. This process is the hallmark of a retrovirus because it reverses the normal flow of genetic information from DNA to RNA.

The new viral DNA is transported into the host cell’s nucleus, where the integrase enzyme inserts it into the host’s chromosome. This integrated viral DNA, now called a provirus, is permanent and turns the cell into a factory for producing more viruses.

The cell’s machinery then transcribes the proviral DNA into messenger RNA (mRNA). Some mRNA strands serve as the genetic material for new viruses, while others create long chains of viral proteins that assemble into immature virus particles.

In the final stage, the immature virion buds from the cell, wrapping itself in a piece of the host’s membrane to form its envelope. After budding, the protease enzyme cleaves the long protein chains into smaller, functional proteins. This maturation makes the virion infectious and ready to repeat the cycle.

Progression from HIV to AIDS

The cycle of HIV replication has a cumulative effect on the immune system, as each new virus budding from a host cell leads to its death. Over years, this continuous destruction results in a steady decline in the overall population of CD4+ cells. The immune system attempts to compensate by producing more CD4+ cells, but it cannot keep pace with the rate of destruction.

This gradual depletion of CD4+ cells progressively weakens the immune system’s ability to mount a defense against other pathogens. As the CD4 cell count falls, the body becomes increasingly vulnerable to opportunistic infections.

Acquired Immunodeficiency Syndrome (AIDS) is the most advanced stage of an HIV infection. A diagnosis of AIDS is made when a CD4+ T-helper cell count drops below 200 cells per cubic millimeter of blood, or if a person with HIV develops one or more specific opportunistic infections.

Interrupting the Viral Cycle with Treatment

The goal of modern HIV treatment, known as antiretroviral therapy (ART), is to disrupt the viral replication cycle. These medications prevent the virus from making copies of itself, reducing the amount of HIV in the body to very low levels. This suppression allows the immune system to recover, increasing the number of CD4+ cells and restoring its ability to fight off infections.

ART involves using a combination of drugs from different classes, with each class targeting a different stage of the viral lifecycle. Entry inhibitors, for instance, work at the beginning of the process. They block HIV from binding to the CD4 receptor or co-receptors, or they prevent the fusion of the viral envelope with the host cell membrane.

Another class of drugs is the reverse transcriptase inhibitors. These medications prevent the reverse transcriptase enzyme from converting the viral RNA into DNA. Without this step, the virus cannot integrate its genetic material into the host cell.

Integrase strand transfer inhibitors (INSTIs) target the integrase enzyme, preventing viral DNA from being inserted into the host cell’s DNA. Protease inhibitors (PIs) work at the end of the cycle by blocking the protease enzyme from cutting the long viral protein chains. This action means new virus particles cannot mature and become infectious. By using a combination of these drugs, ART effectively blocks the HIV life cycle at multiple points, preventing disease progression and transmission.