Benjamin Chen on a New Viral Technology

Fast Moving Front Commentary, May 2011

Benjamin Chen

Article: Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses


Authors: Chen, P;Hubner, W;Spinelli, MA;Chen, BK
Journal: J VIROL, 81 (22): 12582-12595, NOV 2007
Addresses: Mt Sinai Sch Med, Dept Med, Div Infect Dis, Inst Immunol, 1 Gustave Levy Pl,Box 1630, New York, NY 10029 USA.
Mt Sinai Sch Med, Dept Med, Div Infect Dis, Inst Immunol, New York, NY 10029 USA.

Benjamin Chen talks with ScienceWatch.com and answers a few questions about this month's Fast Moving Fronts paper in the field of Microbiology.


SW: Why do you think your paper is highly cited?

Our study supported the idea that infection of T cells through virological synapses is quantitatively and qualitatively different from infection mediated through cell-free virus. It also introduced a new viral technology, a fluorescent genetic clone of HIV, to measure synapse efficiency and to image virological synapses in living cells.

SW: Does it describe a new discovery, methodology, or synthesis of knowledge?

Two T cells engaged in a T cell HIV virological synapse. The infected cell is colored in with rainbow of colors where red colors indicate the concentration of the viral protein Gag and the uninfected cells colored with a red fluorescent dye.
Two T cells engaged in a T cell HIV virological synapse. The infected cell is colored in with rainbow of colors where red colors indicate the concentration of the viral protein Gag and the uninfected cells colored with a red fluorescent dye.

Using a novel method, the study described how cell-to-cell transmission differs from cell-free infection in its efficiency and sensitivity to some inhibitors of infection.

SW: Would you summarize the significance of your paper in layman's terms?

The paper shows that when HIV-infected cells interact with uninfected cells, the virus is efficiently transmitted to the uninfected cells through a specialized pathway that may allow it to evade immune responses.

SW: How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?

Our lab has previously been interested in how HIV assembly is specified to occur at a specific time and place in the cell during infection of immune cells. To study the problem, we needed to develop a method to track HIV-infected cells when they are mixed with uninfected cells in the same test tube. Making a genetic modification of HIV that produces fluorescent virus particles allowed us to follow the virus that was transferred into newly exposed cells using flow cytometry and live cell imaging.

SW: Where do you see your research leading in the future?

Future studies will elucidate signaling pathways in the donor and target cells that allow virological synapses to form. We will also learn how virological synapses participate in the spread of HIV using animal models. We are currently studying so-called humanized mice that can support HIV infection of human immune cells within an immunocompromised mouse. Lastly, and perhaps most importantly, we are studying whether vaccines can be designed to elicit immune responses that are better at blocking cell-to-cell transmission of HIV.

SW: Do you foresee any social or political implications for your research?

We hope that our study of HIV virological synapses may impact the design and evaluation of new vaccines.End

Benjamin K. Chen
Icahn Medical Institute
Mount Sinai School of Medicine
New York, NY, USA

KEYWORDS: HIV-1, TRANSFER, T CELLS, ENV, VIROLOGICAL SYNAPSES, GP41 CYTOPLASMIC TAIL, ENVELOP GLYCOPROTEIN INCORPORATION, DYNAMICS IN-VIVO, NONNEUTRALIZING ANTIBODIES, LYMPHOCYTE COUNTS, TYPE-1 INFECTION, DENDRITIC CELLS, HIV-1 VIRIONS, MURINE CELLS, VIRAL LOAD.

 
 

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