Distinct functions for the membrane-proximal ectodomain region (MPER) of HIV-1 gp41 in cell-free and cell-cell viral transmission and cell-cell fusion

The Journal of Biological Chemistry
Vani G S NarasimhuluPantelis Poumbourios

Abstract

HIV-1 is spread by cell-free virions and by cell-cell viral transfer. We asked whether the structure and function of a broad neutralizing antibody (bNAb) epitope, the membrane-proximal ectodomain region (MPER) of the viral gp41 transmembrane glycoprotein, differ in cell-free and cell-cell-transmitted viruses and whether this difference could be related to Ab neutralization sensitivity. Whereas cell-free viruses bearing W666A and I675A substitutions in the MPER lacked infectivity, cell-associated mutant viruses were able to initiate robust spreading infection. Infectivity was restored to cell-free viruses by additional substitutions in the cytoplasmic tail (CT) of gp41 known to disrupt interactions with the viral matrix protein. We observed contrasting effects on cell-free virus infectivity when W666A was introduced to two transmitted/founder isolates, but both mutants could still mediate cell-cell spread. Domain swapping indicated that the disparate W666A phenotypes of the cell-free transmitted/founder viruses are controlled by sequences in variable regions 1, 2, and 4 of gp120. The sequential passaging of an MPER mutant (W672A) in peripheral blood mononuclear cells enabled selection of viral revertants with loss-of-glycan supp...Continue Reading

References

Jun 1, 1991·AIDS Research and Human Retroviruses·M A MillerR C Montelaro
Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·C P HillW I Sundquist
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·J K MyersJ M Scholtz
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·B LeeR W Doms
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·T Murakami, E O Freed
May 9, 2000·Journal of Virology·S TakikawaT Miyamura
Sep 6, 2000·Trends in Biochemical Sciences·J A Killian, G von Heijne
May 4, 2001·Biochimica Et Biophysica Acta·M B Ulmschneider, M S Sansom
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·A Ono, E O Freed
Aug 19, 2003·The Journal of Biological Chemistry·Pantelis PoumbouriosHeidi E Drummer
Jan 22, 2004·The Journal of Experimental Medicine·Clare JollyQuentin J Sattentau

❮ Previous
Next ❯

Citations

Oct 19, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yi WangMikyung Kim
Apr 20, 2021·ELife·Christophe CaillatWinfried Weissenhorn

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.