Immunopathogenic Mechanisms in Human Immunodeficiency Virus (HIV) Infection

Abstract

An understanding of the immunopathogenic mechanisms of infection with human immunodeficiency virus (HIV) is fundamental in developing successful approaches to designing effective therapeutic and vaccine strategies. In this regard, we have investigated the mechanisms by which HIV inserts itself into the human immune system and uses the elaborate cytokine network to its own replicative advantage. We have also shown that the burden of HIV in CD4+ T cells is directly associated with a decline in this cell population in vivo and a progression to disease. Mononuclear phagocytes may play a role in the pathogenesis of HIV infection by serving as reservoirs of the virus. Of note is the fact that monocytes in the peripheral blood of HIV-infected individuals are rarely infected in vivo, whereas infected-tissue macrophages may play a role in organ-specific HIV-related pathogenesis. The role of HIV-specific humoral and cell-mediated immunity in HIV infection is not well understood. However, fine specificity of responses against HIV have been delineated in some in-vitro systems. It is unclear why these responses, particularly HIV-specific cytolytic T-cell responses, diminish over the course of infection and are unable to contain progression of infection.

Priming-Boosting Vaccination with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin and a Nonreplicating Vaccinia Virus Recombinant Leads to Long-Lasting and Effective Immunity

“…Because long-term survival in humans has been observed when HIV-1 replication is controlled by protective immunity (12,29), targeted experimental immunogens have been designed to closely mimic the long-lasting protective immunity induced in long-term human survivors by the natural infection (8,25). Recently, various vaccine modalities, including live viral vectors and DNA, have been used to elicit protective immunity in nonhuman primate models (9).…”

Neuropsychological abnormalities in AIDS and asymptomatic HIV seropositive patients.

“…2 Apart from cases of overt dementia, a high percentage of patients with AIDS and a smaller, but substantial number of patients with AIDS related complex (ARC) exhibit some degree of cognitive impairment for which no opportunistic or other causes can be found. 34 In a few cases (5-10%) the appearance of a clinically significant cognitive decline is the event which signals the development of symptomatic immunodeficiency.…”

Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro.

“…Symptomatic HIV infection exhibits many hallmarks of systemic immune activation, including cytokine dysregulation and T cell stimulation (1)(2)(3)(4). The life cycle of HIV-1 is particularly well-adapted to a host environment of chronic, active T cell stimulation.…”

“…Of the encoded regulatory proteins essential for high level HIV replication, Rev, Tat, and Nef are known to interact, directly or indirectly, with induced cellular factors (12,13). In addition to regulatory protein-protein interactions, the long terminal repeat (LTR) 1 transcriptional promoter region of HIV contains sequence homology to several DNA-binding sites for cellular proteins that are involved in regulation of T cell gene transcription. LTR homologous binding sites exist for Sp-1, Oct-1, AP-1, NF-AT, NF-k B, and NRE (12), all of which are induced during the process of T cell activation.…”