Pathogenesis of Immunodeficiency Virus Infections
Guido Poli and Volker Erfle
from: Retroviruses: Molecular Biology, Genomics and Pathogenesis (Edited by: Reinhard Kurth and Norbert Bannert). Caister Academic Press, U.K. (2010)
Extensive analysis of naturally occurring simian immunodeficiency viruses (SIVs) and comparative phylogenetic studies with human immunodeficiency viruses (HIVs) suggests that the latter are close relatives of the SIVcpz viruses of chimpanzees (HIV-1) or the SIVsmm viruses of sooty mangabys (HIV-2). Crossing of species barriers resulted in adaptation to the human host and subsequent acquisition of a pathogenic phenotype. Naturally occurring T lymphocyte-tropic lentiviral infections are highly prevalent and productive but are not usually pathogenic for native hosts. Crossing species barriers may produce an abortive infection or, as in the case of the HIVs, may enhance virulence after several cycles of transmission. The large number of species carrying these viruses may suggest that infection confers an evolutionary advantage to the host. The virulent T-lymphocyte-tropic lentiviruses have a similar genomic structure and exhibit comparable replication strategies. Their major targets are lymphocytes populating lymphoid organs and tissues, and antigen-presenting cells (dendritic cells, mononuclear phagocytes). Within these targets the virus can replicate to very high titres and thereby exhaust CD4+ T cells, producing profound immunodeficiency. Although the infection of lymphoid organs and tissue is the pathologic hallmark of HIV infection, this virus also infects cells of the central nervous system. This chapter discusses various pathogenic mechanisms involved in immune activation and dysregulation, and summarises characteristics of HIV/SIV gene-host factor interaction in the immune and central nervous systems read more ...