A Dual Role for Tetherin

One thing that seems pretty clear at this meeting is that the study of host cell restriction factors that inhibit viral replication or infection (such as Trim5α and tetherin) has been literally exploding in the past ten years. “There has been a remarkable gold rush in interest in restriction factors,” said Jonathan Stoye, a virologist from the MRC National Institute for Medical Research in London, in his Keynote address on Wednesday. He said that in 2000, the Cold Spring Harbor Retrovirology meeting featured just two talks on such factors, whereas this year, more than a quarter of the talks were about restriction factors.

One topic discussed here on Thursday was whether restriction factors can have additional functions. Last year, Jeremy Luban’s group at the University of Geneva reported that the host restriction factor Trim5 also functions as a pattern recognition receptor (PRR), in that it activates an innate immune response when it encounters HIV (Nature 472,361,2011).   

Luban told IAVI Report at the time that other host cell restriction factors such as tetherin might also act as PRRs (see A Flurry of Updates from Keystone, IAVI Report, March-April 2011).   

On Thursday, several groups reported evidence suggesting that Luban was right: Tetherin can indeed activate an innate immune response. For example, Stuart Neil from King’s College London reported that human primary CD4+ T cells infected with tetherin-sensitive HIV-1 (which doesn’t have Vpu to counteract tetherin) produce more proinflammatory cytokines.“This is going to be a recurring theme [that] antiviral factors by their nature can be pattern recognition receptors as well,” Neil said, adding that this is advantageous for the organism, because it makes infected cells much more visible to the immune system.  

Talking science wasn’t the only thing scientists could be seen doing on Thursday. In the evening, Nathaniel Landau, a virologist from New York University, played Jazz guitar with three recent graduates of the Manhattan School of Music. Perhaps not surprisingly, Landau decided to call the band playing that night “The Pseudotypes,” which is the scientific term for viruses that carry viral Envelope proteins from different viruses.