Virus phenotype switching and disease progression in HIV-1 infection.

Autor: Callaway DS; The Wellcome Trust Centre for the Epidemiology of Infectious Diseases, Department of Zoology, University of Oxford, UK., Ribeiro RM, Nowak MA
Jazyk: angličtina
Zdroj: Proceedings. Biological sciences [Proc Biol Sci] 1999 Dec 22; Vol. 266 (1437), pp. 2523-30.
DOI: 10.1098/rspb.1999.0955
Abstrakt: One of the phenotypic distinctions between different strains of human immunodeficiency virus type 1 (HIV-1) has to do with the ability to cause target cells to form large multinucleate bodies known as syncytia. There are two phenotypes according to this characterization: syncytium-inducing (SI) and non-syncytium-inducing (NSI). NSI strains are usually present throughout infection, while SI strains are typically seen at the beginning of the infection and near the onset of AIDS. The late emergence of SI strains is referred to as phenotype switching. In this paper we analyse the factors that lead to phenotype switching and contribute to the dynamics of disease progression. We show that a strong immune system selects for NSI strains while a weak immune system favours SI strains. The model explicitly accounts for the fact that CD4+ cells are both targets of HIV infection and crucial for activating immune responses against HIV In such a model, SI strains can emerge after a long and variable period of NSI dominated infection. Furthermore, versions of the model which do not explicitly account for HIV-specific, activated CD4+ cells do not exhibit phenotype switching, emphasizing the critical importance of this pool of cells.
Databáze: MEDLINE