DiagnosticsThe Cytoplasmic Talk Of Retroviruses Helps Them Spread From Cell To Cell
It is known that Retroviruses, such as HIV, that are already within cells
are much more easily transmitted when they spread through direct contact
between cells than if they are floating free in the blood stream. However,
how this contact stimulates virus- spreading has up until now been poorly
understood. In this week"s edition of the online open-access journal PLoS
Biology, researchers at Yale University, led by Dr. Walther Mothes, have
recorded movies of viral activity within cells that helps explains why
cell-to-cell transmission is so efficient and may in turn provide insights
into
potential targets for a new generation of Anti-Retroviral drugs.
"Cell-to-cell transmission is a thousand times more efficient, which is
why diseases such as AIDS are so successful and so deadly," said Walther
Mothes, associate professor of microbial pathogenesis at the Yale School
of Medicine. "And because retroviruses spread through the tight cell-cell
interface, they are out of reach for the immune system."
Using imaging technology that can track individual virus particles in real
time, the team discovered that retrovirus-infected cells can specifically
assemble daughter viruses at the point of contact between cells. Ten times
more of these particles are found at these cellular connection points than
elsewhere at the surface of cells, the researchers report. The ability of
infected cells to specifically produce viruses only at cell interfaces
offers an explanation of how viruses spread so efficiently. The team
identified a clue to how virus assembly is targeted to these points of
contact:
it involves a sticky viral protein called Env that docks with uninfected
cells and then attracts the viral particles to these sites. If this
adhesion
molecule lacked a key element, a "cytoplasmic tail," then the viral
particles did not assemble at the patches of contact between cells.
Mothes expects many more such targets will be identified as scientists
work out the mechanics of cell-to-cell transmission. "We are just opening
the
door to this whole process," Mothes said. "It is a black box and many,
many cellular factors have to be involved in making this happen. Our hope
is that somewhere down the road we will have a completely new anti-viral
strategy based on targeting cell-to-cell transmission."
Funding:
The work is supported by a grant from the National Cancer
Institute ROI CA098727 to WM and a fellowship from amfAR Foundation for
AIDS
research to JJ. The funders had no role in the study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
Competing interests statement:
The authors declare that no competing
interests exist.
Citation:
"Assembly of the Murine Leukemia Virus Is Directed towards Sites of Cell-Cell Contact."
Jin J, Sherer NM, Heidecker G, Derse D, Mothes W (2009)
PLoS Biol 7(7): e1000163. doi:10.1371/journal.pbio.1000163
PLoS Biology