The Induction of Immunosuppression by HIV Viral Particles

Multifactorial Nature of HIV-Associated Immunosuppression

The immunosuppressive effects of HIV infection extend beyond the virus’s direct cytopathic impact on lymphoid cells. Rather than solely the result of viral destruction of T cells, HIV-induced immunosuppression appears to operate through two fundamental mechanisms.

Immune Regulation via Cytokine Induction

First, several HIV-encoded proteins stimulate the production of immunosuppressive cytokines, most notably transforming growth factor beta (TGFβ) and interleukin-10 (IL-10). These cytokines act as pleiotropic regulators, exerting stimulatory and inhibitory effects on numerous immune functions. Their overproduction creates a dysregulated immune environment, compromising the host’s ability to mount effective immune responses against the virus and other pathogens.

Direct Suppression of Immune Pathways by Viral Proteins

Second, HIV proteins—including TAT, NEF, VPR, p24, and gp120—directly interfere with various immunological pathways. These proteins act at multiple levels to suppress innate and adaptive immunity, undermining antiviral defenses and broader immune surveillance.

Later in the infection cycle, the viral matrix protein p17 may contribute to immune dysregulation in a different manner. Rather than suppressing immunity, p17 may induce inappropriate activation of cell-mediated immune responses. This aberrant stimulation is associated with the release of pro-inflammatory cytokines, a reduction in IL-16 synthesis, and, ultimately, neuroinflammatory processes that contribute to HIV-associated dementia.