Human Immunodeficiency Virus (HIV) is a retrovirus that systematically attacks the immune system. This viral invasion weakens the body’s natural defenses, leaving it vulnerable to various infections and diseases. Understanding how HIV invades and compromises the immune system is central to grasping its devastating impact. The virus targets specific immune cells, replicates within them, and sets the stage for progressive immune decline.
HIV’s Primary Targets
HIV primarily targets specific immune cells, most notably CD4+ T helper cells. These cells are crucial for orchestrating the immune response, signaling other immune cells to fight infections. Their destruction directly impairs the body’s ability to defend against pathogens.
HIV also infects other immune cells, including macrophages and dendritic cells. Macrophages engulf cellular debris and pathogens, while dendritic cells present antigens to T cells, initiating immune responses. These cells possess the CD4 receptor and co-receptors necessary for viral entry, allowing HIV to establish infection.
Cellular Entry Mechanisms
HIV enters a host cell through a multi-step mechanism. The viral envelope glycoprotein, gp120, first binds to the CD4 receptor on target immune cells. This initial binding induces a conformational change in gp120, exposing a site that then interacts with a co-receptor.
Co-receptors are either CCR5 or CXCR4, and the specific co-receptor used by HIV influences which cell types it can infect. This co-receptor binding triggers further structural changes in the viral envelope, exposing another glycoprotein called gp41. The exposed gp41 then facilitates the fusion of the viral membrane with the host cell membrane. This fusion allows the viral core, containing the genetic material and enzymes, to enter the host cell’s cytoplasm.
Replication and Viral Production
Once the viral core enters the host cell’s cytoplasm, the HIV life cycle continues with reverse transcription. The viral enzyme reverse transcriptase converts HIV’s single-stranded RNA genome into a double-stranded DNA copy. This newly synthesized viral DNA, known as a provirus, then moves into the host cell’s nucleus.
Inside the nucleus, another viral enzyme, integrase, integrates this viral DNA into the host cell’s genetic material. Once integrated, the host cell’s machinery transcribes the viral DNA into new viral RNA molecules. These RNA molecules serve as templates for viral proteins and also as the genetic material for new viral particles.
The newly produced viral RNA and proteins assemble near the host cell’s membrane, forming immature viral particles. These particles bud off from the host cell, acquiring a piece of the host cell’s membrane as their outer envelope. A viral enzyme called protease then cleaves the long protein chains within the immature virus, creating mature, infectious HIV virions capable of infecting more cells.
Immune System Evasion
HIV employs strategies to evade detection and destruction by the host’s immune system. One mechanism is its high mutation rate, driven by the error-prone reverse transcriptase enzyme. This constant genetic change allows HIV to alter its surface proteins, making it difficult for the immune system to recognize and eliminate the virus.
Another evasion tactic is latency, where integrated viral DNA (provirus) remains dormant within the host cell’s genome. In this latent state, the virus does not actively produce new viral particles or proteins, rendering it invisible to immune surveillance and resistant to antiretroviral therapies. Infected cells can later reactivate, leading to renewed viral production. HIV also impairs immune cell function by downregulating Major Histocompatibility Complex (MHC) class I molecules on infected cells, which are essential for presenting viral antigens to cytotoxic T lymphocytes.
Progressive Immune Depletion
The continuous cycle of HIV infection and replication leads to a gradual destruction of CD4+ T cells. As these immune cells decline, the immune system progressively weakens. This diminishing capacity to fight pathogens leaves individuals susceptible to a wide range of infections that would not threaten a healthy person.
These are known as opportunistic infections, taking advantage of the compromised immune state. Without effective treatment, progressive immune depletion ultimately leads to Acquired Immunodeficiency Syndrome (AIDS). An AIDS diagnosis is made when the CD4+ T cell count falls below a certain threshold or when specific opportunistic infections or cancers develop.