On SAMHD1, Virological Synapses, and Hapmapoly

It was at this meeting last year when researchers first announced SAMHD1 as the cellular restriction factor that is the target of HIV Vpx (see Research Briefs, IAVI Report, May-June 2011). 

The original studies of SAMHD1 suggested that expression of SAMHD1 in dendritic cells and macrophages is the reason why these cells can’t be easily infected with HIV-1. In a session here yesterday, which was entirely devoted to SAMHD1, Hanna-Mari Baldauf from the University of Heidelberg in Germany presented evidence suggesting that SAMHD1 expression may also be a reason why resting CD4+ T cells from peripheral blood are resistant to productive HIV-1 infection.   

It’s still unclear, however, why activated CD4+ T cells, the primary target for HIV-1 infection, are easy to be productively infected with the virus even though they also express SAMHD1. One possible explanation, Baldauf said, could have to do with the way SAMHD1 inhibits HIV-1 replication: It degrades dNTPs, the building blocks the HIV reverse transcriptase needs to synthesize DNA from HIV-1 RNA. Because activated CD4+ T cells seem to have higher levels of dNTPs than resting CD4+ T cells, these higher dNTP levels could explain why activated CD4+ T cells can still produce HIV-1 even though they express SAMHD1.   

The final session of the meeting today featured some interesting news for anyone interested in virological synapses, sites of cell-cell contact through which HIV and other retroviruses can be transmitted from cell to cell. Xaver Sewald from the lab of Walther Mothes at Yale University School of Medicine showed the first in vivo evidence for such synapses, for Murine Leukemia Virus. He observed the synapses in lymph nodes of living mice, using fluorescently labeled cells and virions. “This is the first proof of principle that in vivo you see these structures,” Sewald said. Mothes said he plans to use a similar approach to look for in vivo evidence of virological synapses involved in HIV transmission.   

Finally, have you ever heard the word Hapmapoly? If not, don’t worry, because the word (a combination of the words hapmap and monopoly) only exists here at the bar of Cold Spring Harbor Laboratories. It’s the name of a modified version of the game Monopoly for geneticists I found hanging on the wall there (see image below).