Evidence for the HIV-1 phenotype switch as a causal factor in acquired immunodeficiency

Svetlana Glushakova, Jean Charles Grivel, Wendy Fitzgerald, Andrew Sylwester, Joshua Zimmerberg, Leonid B. Margolis

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Both cellular and humoral immunodeficiency develop in vivo after prolonged infection with HIV-1, but the mechanisms are unclear. Initial infection with HIV-1 is transmitted by macrophage (M)-tropic/non-syncytia- inducing (NSI) viruses, which hyperactivate the immune system, and, in one view, cause immunodeficiency by 'exhaustion' of lymphoid tissue. An alternative hypothesis is that immunodeficiency is caused by the replacement of M-tropic viruses by T cell (T)-tropic/syncytia-inducing (SI) viruses, which are known to be highly cytopathic in vitro and emerge late in infected individuals around the time of transition to AIDS (refs. 1, 7-9). To test these two possibilities, we have developed an ex vivo model of humoral immunity to recall antigens using human lymphoid tissue. This tissue supports productive infection with both M- and T-tropic HIV-1 isolates when cultured ex vivo. We found that specific immune responses were enhanced by productive infection of the tissue with M-tropic/NSI HIV-1 isolates, but were blocked by T-tropic/SI HIV-1 isolates. The mechanism involves specific irreversible effect on B-cell activity. Our results support the hypothesis that the phenotype switch to T-tropic viruses is a key determinant of acquired humoral immunodeficiency in patients infected with HIV.

Original languageEnglish (US)
Pages (from-to)346-349
Number of pages4
JournalNature medicine
Volume4
Issue number3
DOIs
StatePublished - Apr 14 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Evidence for the HIV-1 phenotype switch as a causal factor in acquired immunodeficiency'. Together they form a unique fingerprint.

  • Cite this

    Glushakova, S., Grivel, J. C., Fitzgerald, W., Sylwester, A., Zimmerberg, J., & Margolis, L. B. (1998). Evidence for the HIV-1 phenotype switch as a causal factor in acquired immunodeficiency. Nature medicine, 4(3), 346-349. https://doi.org/10.1038/nm0398-346