Role of cell-to-cell transmission in sustaining the HIV reservoir
1 August 2012. Related: Basic science and immunology.
Richard Jefferys, TAG
A new study by Marc Permanyer and colleagues, published online recently by the Journal of Virology, disputes the interpretation of results suggesting that cell-to-cell transmission facilitates ongoing viral replication in the face of antiretroviral therapy. [1]
The earlier research, from the laboratory of David Baltimore, was published as a high profile paper in August 2011 in the journal Nature. This paper proposed that cell-to-cell transmission might represent a mechanism that sustains the reservoir of HIV-infected cells in people on long-term ART. [2]
The essence of the disagreement relates to the method used to measure cell-to-cell HIV spread in a laboratory culture system. The original study used a modified HIV that expresses a green fluorescent protein (GFP) tag, and assessed whether the tag became detectable in cells as a surrogate for viral replication.
Permanyer’s work shows that transfer of HIV from cell-to-cell, as measured by GFP, does not necessarily equate to continuation of the viral replication cycle. In the presence of ART, the transfer is shown to be abortive because replication is blocked.
The researchers conclude: “data on cell-to-cell spread should be taken with caution as it is crucial to correctly distinguish and measure abortive virus transfer or subrogate markers of infection (LTR-driven GFP) from effective viral replication.”
Source:
TAG Basic Science Web Blog (29 Jun 2012).
http://tagbasicscienceproject.typepad.com/
References:
- Baltimore J et al. Nature, August 2011.
- Permanyer M et al. Antiretroviral agents effectively block HIV replication after cell to cell transfer. J Virol. 2012 Jun 13. [Epub ahead of print]
http://jvi.asm.org/content/early/2012/06/08/JVI.01044-12.abstract