Can HIV-1 Entry Sites Be Deduced by Comparing Bulk Endocytosis to Functional Readouts for Viral Fusion?

• Type of Material: Article
• Authors: Mariana Marin, Emory University; Gregory Melikian, Emory University
• Language: English
• Date: 2015-03-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2015, American Society for Microbiology.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.03352-14
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 89
• Issue: 5
• Start Page: 2985
• End Page: 2985
• Research Categories: Health Sciences, General; Biology, Virology

Abstract

A recent Journal of Virology article by Herold and colleagues (1) addresses the controversial issue of the HIV-1 entry pathways. Two lines of evidence led the authors to conclude that internalized viruses do not contribute to productive HIV-1 entry into lymphoid cells. First, a dominant-negative dynamin mutant blocked HIV-1 uptake but not fusion. Second, preincubation at 22°C allowed virus endocytosis while preventing fusion/infection. Subsequent fusion induced by raising the temperature could be fully blocked by membrane-impermeable peptide inhibitor T20, demonstrating that productive endocytosis did not occur at 22°C. The latter result fully agrees with our data showing that HIV-1 engages CD4 and coreceptors on the cell surface upon incubation at reduced temperatures (2, 3). However, we interpreted the subsequent fusion induced by shifting to 37°C as synchronized endocytosis followed by fusion with endosomes, since the virus escape from the low-temperature block was delayed compared to escape from a T20-like peptide (2).