Adjunct Professor, Department of Pathobiology
Member, Division of Basic Sciences, Fred Hutchinson Cancer Research Center
Research Professor, Department of Microbiology
http://myprofile.cos.com/mlinial
Ongoing studies in the lab focus on the foamy viruses (FV), a subfamily of
Retroviridae with unusual properties. We are interested in both the details
of the replication pathway of this remarkable viral group, as well as their
interactions with the host. Foamy viruses are distinguished from other retroviruses
(Orthoretroviruses), such as HIV, in many ways. We are interested in properties
of the FV enzymes including integrase and reverse transcriptase (RT). We have
previously found that RT is highly active and processive, thus FV RT has potential
as a new laboratory reagent for cDNA synthesis. The FV assembly properties
are quite interesting as well. We have found that virions assemble near the
centriole, where they encounter the viral glycoproteins which then allows budding
from the cell. We are currently trying to understand which cell proteins are
involved in assembly, and the effects of mutations in the Gag protein on this
process. Foamy viruses are unique amongst retroviruses in that infection invariably
leads to lifelong persistence without pathology. FV are ubiquitous in non-human
primates (NHP). We are studying the host responses to foamy virus infection,
and the ability of the virus to sustain a life-long persistent but nonpathogenic
infection. We have examined the effects of immunosuppression in rhesus macaques
(via SIV or antibody depletion of immune cell types) on foamy virus replication.Contrary
to what was previously believed, we have found high levels of viral RNA in
most oropharyngeal tissues in normal animals, suggesting that viral infection
is not completely latent. Further, SIV immunosuppression leads to FV replication
in other tissues such as the small intestine, raising the possibility that
in NHP, FV could be involved in progression to AIDS. Finally, there have
been several recent studies monitoring transmission of foamy viruses from NHP
to humans, which occurs fairly frequently. In collaboration with a Lisa-Jones
Engel at the University of Washington Primate Center, we have been looking
at FV transmission in southeast Asia. We have found a number of humans who
are infected with FV, including the first NHP pet owner. FV appear to be a
good sentinel for monitoring human infection from interaction with NHP, as
they are the most easily transmitted virus.