Title:HIV Extracellular Tat: Myth or Reality?
Volume: 13
Issue: 2
Author(s): Erwann Loret
Affiliation:
Keywords:
HIV, HIV DNA, reservoirs, sanctuary, Tat, vaccine.
Abstract: The human immunodeficiency virus type 1 (HIV) eradication will require
elimination of HIV infected cells. No antiretroviral treatments (ART) or vaccine approaches
have been able to reduce significantly the level of HIV infected cells in peripheral blood.
This inefficacy is generally explained by the presence of a major reservoir of latent HIV
infected cells in the central nervous system (CNS) that would be a sanctuary where
Cytotoxic T Lymphocytes (CTL) have no access and would refresh peripheral blood with
activated HIV infected cells. In this review, the presence of a major reservoir in the CNS appears to be
inconsistent with recent clinical studies measuring HIV DNA. The major reservoirs are gut tissue, rectal tissue
and the peripheral blood where HIV infected cells survive in an environment containing CTL. Extracellular
Tat might protect HIV infected cells from CTL due to its capacity to cross CTL membranes and trigger
apoptosis. Evidences of Tat secretion from HIV infected cells are shown with the detection of Tat antibodies
in different clinical studies. Presence of neutralizing Tat antibodies in cohorts of patients who were exposed to
HIV but who are now seronegative is described. The conclusion of this review is that a vaccine eliciting
neutralizing antibodies against Tat might significantly reduce the level of HIV infected cells, what ART or
other vaccine approaches have been unable to achieve now. It could be a first step towards HIV eradication.
