Novel view of HIV entry could lead to newly designed drugs

May 1st, 2009 - 3:05 pm ICT by ANI  

Washington, May 01 (ANI): It looks like scientists will have to rethink the design of drugs which are meant for blocking HIV from infecting human cells, for a new research has shown HIV doesn’t enter cells in the way that experts had generally assumed it did.

The new research has shown that rather than fusing directly with the plasma membrane at cells’ outer surfaces to release its contents, HIV fusion primarily occurs via smaller, membrane-bound compartments inside of cells known as endosomes.

The discovery suggests that anti-HIV drugs known as fusion inhibitors might be more effective in blocking HIV if they too can do their work inside of cells, where fusion takes place.

“We show that HIV fusion occurs virtually exclusively from endosomes. It appears that it is this path to entry that leads to infection,” said Gregory Melikian of the University of Maryland School of Medicine.

“In order to efficiently block intracellular fusion events, the next generation of HIV entry inhibitors must be able to permeate the cell membrane,” he added.

In the new study, Melikian and his colleagues relied on a series of imaging studies to literally watch as HIV-1, the virus that normally infects humans, enters cells.

Those experiments showed that complete viral fusion occurs not on the cell surface, but in endosomes. While HIV’s envelope sometimes did mix with the cell’s plasma membrane, in those cases delivery of the viral contents did not occur.

“Time-resolved imaging of single viruses and differential blocking of fusion by site-specific and universal inhibitors revealed that HIV-1 co-opts the endocytic machinery to enter into and fuse with target cells,” the researchers said.

“By contrast, fusion with the plasma membrane did not progress beyond the lipid mixing step, suggesting that endosomal entry is the pathway that leads to productive infection,” they added.

The study appears in the May 1st issue of the journal Cell, a Cell Press publication. (ANI)

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