HIV and the Mucosa: No Safe Haven

Abstract

Since its discovery in 1983, Human Immunodeficiency Virus-1 (HIV) infection has resulted in the death of several million people worldwide. Control of the spread of HIV infections is one of the major concerns of the scientific community today. This retrovirus houses a genome encoding three viral structural proteins: group-specific antigen, polymerase and envelope. The envelope gp120 binds to cell surface receptors on susceptible target cells in the host. Although HIV is known to infect various cell types, cells expressing the CD4 receptor support high levels of viral replication in vivo. Gastrointestinal complications are commonly seen in patients with HIV-1 infections progressing to AIDS. Recent studies have shown that HIV causes massive disruption of the Gut Associated Lymphoid Tissue (GALT) very early in infection. Intestinal dysfunction is often not resolved despite the success of HAART in improving the clinical status of these patients. GALT supports robust viral replication in mucosal memory CD4+ T cells during primary HIV infection, leading to a severe depletion of the CD4+ T cells which persists through all stages of HIV infection in the absence of therapeutic interventions. Functional genomic analysis of host responses to HIV shows that molecular processes regulating inflammation and immune activation are dominantly expressed in GALT of therapy-nave HIV-1 infected patients with a progressive clinical course. Heterosexual transmission is the primary mode for the spread of HIV infection and the virus gains entry through mucosal surfaces and infects susceptible target cells. Since a majority of new infections are acquired through the mucosal route, induction of mucosal immunity is an important factor in vaccine design.