Isolation and biological characterization of infectious molecular clones of HIV-1 subtype-C with expanded coreceptor usage from an Indian demented subject

Abstract

Twenty five years following its discovery, Human Immunodeficiency Virus (HIV) - the causative agent of Acquired Immuno Deficiency Syndrome (AIDS), still remains a major threat to human beings. The most widely recognized consequence of HIV-1 infection is the slow and progressive deterioration of the integrity and function of the immune system. Although the clinical presentation of HIV-1-associated immune system dysfunction varies from individual to individual, the infection, without therapeutic intervention, generally unfolds in three phases over a period of approximately six to ten years after initial exposure to the virus: acute infection (lasting approximately three months), clinical latency (lasting typically eight to ten years), and clinically apparent disease (lasting two to three years) (Pantaleo, G et al., 1993). The acute phase is characterized by a large, but transient viremia within the peripheral circulation and sometimes an acute mononucleosis-like syndrome. During clinical latency, there is a slow but steady decline in the number of CD4-positive T lymphocytes and in the general integrity of the immune system, a very low level of detectable virus within the peripheral blood, and a concurrent decrease in the titer of antiviral antibodies (Pantaleo, G et al., 1993). During this period, HIV-1 replication is readily detectable in the lymph nodes despite almost undetectable levels of plasma virus (Pantaleo, G et al., 1993, 1991, Embretson, J et al., 1993). The clinically apparent phase of disease is typified by the reappearance of HIV-1 viremia, a precipitous loss of CD4-positive T lymphocytes, a rapid decline in immune function, and numerous AIDS-defining illnesses (Katzenstein DA et al., 1996). Although the rate of the disease progression is highly variable among HIV patients, most infections follow a typical course that can be divided into three stages. Primary HIV-infection, clinical latency, and clinically apparent disease as described above and as shown in Figure1.1. Without pharmacotherapeutic intervention, the ultimate outcome of this phase is death for a vast majority of infected individuals.