Regulation of Human Immunodeficiency Virus Infection: Implications For Pathogenesis

Despite the intensive investigation, much remains to be learned about the sequence of events leading to the development of the acquired immunodeficiency virus syndrome (AIDS) following human immunodeficiency virus (HIV) infection. The development of AIDS is the culmination of a progressive infection with HIV, whose course and outcome are determined by the interactions between viral and host cellular factors, possibly influenced by additional agents or “cofactors”. One important factor in disease progression is the extent of viral replication at various times of postinfection. While the nature and effectiveness of the host immune response clearly play important roles in determining the amount of HIV replication, intrinsic viral factors also contribute. The cytopathicity and tropism of HIV isolates vary during the course of disease and may be important in the progression of AIDS. Furthermore, the amount of virus replication is a direct result of the molecular regulatory pathways governing the HIV gene expression. Efficient HIV gene expression results in abundant production of progeny viral particles, with the potential for increased infection of CD4+ T lymphocytes. Conversely, low-level HIV production may lead to the establishment of “latent” reservoirs of HIV, resulting in persistence or chronicity of infection. This chapter focuses on the aspects of HIV molecular biology and gene expression that influence the degree of viral production. The molecular mechanisms, by which the host cellular factors and heterologous infectious agents augment (or in some cases inhibit), HIV gene expression are discussed and the potential role that these various regulatory influences play in the progression of HIV infection is considered in this chapter. This chapter focuses on the regulation of HIV-1, the predominant cause of HIV disease in the world; HIV-2, a much rarer cause of AIDS, shares many of the same regulatory pathways of HIV-1.