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HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell

Boullé, Mikaël and Müller, Thorsten G. and Dähling, Sabrina and Ganga, Yashica and Jackson, Laurelle and Mahamed, Deeqa and Oom, Lance and Lustig, Gila and Neher, Richard A. and Sigal, Alex. (2016) HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell. PLoS Pathogens, 12 (11). e1005964.

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Abstract

Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Computational Modeling of Biological Processes (Neher)
UniBasel Contributors:Neher, Richard
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1553-7366
e-ISSN:1553-7374
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:16 Sep 2019 08:24
Deposited On:25 Oct 2017 12:31

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