Contents - College of Medical and Dental Sciences - University of ...

The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Immunology I Abstract 9
KSHV K5 COUNTERACTS TETHERIN, A NOVEL COMPONENT OF INNATE
ANTIVIRAL IMMUNITY, TO FACILITATE VIRUS RELEASE
Edward Tsao 1 , Sam Wilson 1 , Claire Pardieu 1 , Ben Webb, Imogen Lai, Stuart Neil 2 , Greg
Towers 1 , and Paul Kellam 1
1. MRC Centre for Medical Molecular Virology, Department of Infection, UCL, 46
Cleveland Street, London W1T 4JF; 2. Peter Gorer Department of Immunobiology, 2nd
Floor, Borough Wing, Guy's, King's and St Thomas' Hospitals, King's College London,
Great Maze Pond, London SE1 9RT
Abstract
Tetherin (also called CD317, BST2, or HM1.24) has been identified as an interferoninducible
human factor that inhibits the release of retroviruses, and its antiviral effect can
be antagonised by HIV-1 vpu. It has been postulated that tetherin, a membraneassociated
protein, is present both on plasma membranes and viral envelopes (acquired
from the host membrane through viral budding). The interaction between virion- and
cell-associated tetherin molecules not only prevents virus release, but may also lead to
endocytotic internalisation of the virions and their subsequent degradation. This model
suggests that tetherin would be effective against all enveloped viruses. A recent
proteomic study revealed that the levels of tetherin were strongly reduced in HeLa cells
expressing KSHV K5. Here we show that 1) tetherin is expressed in PELs, that 2) KSHV
K5 is required for the efficient release of virions from cells, and 3) in the absence of K5,
the reduction of tetherin expression using shRNA rescues virus release. This is the first
study to show that tetherin is active against enveloped DNA viruses, supporting the
notion that it is an indiscriminate antiviral factor acting against enveloped viruses.
Presenting author Email: e.tsao@ucl.ac.uk
30