HIV Without AIDS: The Immunological Secrets of Natural Hosts

Human Immunodeficiency Virus (HIV) infection causes Acquired Immune Deficiency Syndrome (AIDS), while its ape and monkey progenitor Simian Immunodeficiency Virus (SIV) does not cause AIDS in its nonhuman primate natural reservoir hosts. Astonishingly, AIDS is avoided despite findings in a number of these host primate species indicating they too harbor high levels of virus replication that kills off CD4 T cells. These primate species that are so called “natural hosts” of SIV, essentially have HIV without ever getting AIDS. The elucidation of the exact mechanisms allowing natural SIV hosts to avoid disease progression may prove decisive in the battle to understand HIV pathogenesis for the purpose of preventative or curative HIV and AIDS therapy. Comparative studies in natural and nonnatural hosts of lentiviral infections (i.e. HIV or SIV) have defined essential distinguishing features, opening up new avenues for possible therapeutic and preventative intervention. In this chapter, we will describe recent and past breakthroughs that come from comparing lentiviral infections in AIDS-free natural hosts, to immunocompromised nonnatural hosts. In addition, we will discuss how the knowledge derived from the study of natural hosts may inform the design of novel therapies and vaccine strategies for HIV-infected humans.