Insights on Cell-Cell Transmission of HIV and the Flexibility of HIV Envelope

HIV can be transmitted as a free particle, or from cell to cell, for example between CD4+ T cells, through so-called virological synapses. One question is why HIV particles are budding preferentially in such synapses. At today’s session on retroviral entry mechanisms, Clare Jolly from the University College London reported that the reason seems to be that the cell-cell contact induces polarization of the infected donor cell, in that the microtubule organizing center migrates towards the site of cell-cell contact. This suggests that HIV proteins probably migrate along microtubules towards the virological synapse, which could explain why HIV particles preferentially bud there. 

The session also featured an interesting talk by Kelly Lee from the University of Washington, who looked at the flexibility of different parts of glycosylated gp120. To do so, he soaked gp120 in heavy water, which contains deuterium instead of hydrogen, for one minute. He then used mass spectrometry to measure how much of the heavy water had been incorporated into the different parts of gp120—the more heavy water had been incorporated, the more flexible (or less rigid) were the parts of gp120. 

Lee found that gp120 taken from different strains of HIV showed a remarkable variability in their flexibility. He also showed that CD4 binding site antibodies like b12 bind better to more rigid versions of gp120. This suggests, Lee said, that one reason why neutralizing antibodies neutralize some HIV strains less well could be that the CD4 binding site of their gp120 is less rigid (or more flexible).