A****7
发帖数: 902 | 1 https://www.med.unc.edu/microimm/directory/ralph-baric-phd-1/
Ralph Baric, PhD
Professor
Department of Epidemiology
3304 MHRC, School of Public Health
919-966-3895
Research
Most of the research in our laboratory has used coronaviruses as models to
study the genetics of RNA virus transcription, replication, persistence, and
cross species transmission. We have also been using alphavirus vaccine
vectors to develop novel candidate vaccines against caliciviruses. Specific
areas of interest include:
1. Coronavirus Reverse Genetics and vaccine development.
We have developed infectious cDNAs from two coronaviruses. Specific
applications include: a) studying critical cis and trans acting factors that
regulate coronavirus subgenomic mRNA synthesis and replication, b)
rearranging the coronavirus gene order to study genome evolution and
function in coronavirus transcription and replication, c) identification of
the minimal coronavirus genome, d) development of coronavirus replicon RNAs
and coronavirus replicon particles for vaccine development, e) expression of
heterologous genes from coronavirus vaccine vectors for swine and other
important species.
2. Norwalk like virus (Calicivirus) vaccine development.
We are using the alphavirus, Venezuelan equine encephalitis virus (VEE), as
a vaccine vector for the Norwalk like viruses. Our research encompasses: a)
expression of Norwalk and SnowMountain virus capsid proteins from VEE, b)
biochemical and immunologic characterization of these recombinant proteins,
c) vaccine testing in mice, and d) use a human challenge model to identify
immunologic responses associated with protection from NLV reinfection.
3. RNA virus transcription, replication and recombination.
Our laboratory has had a longstanding interest in using genetic approaches
to study coronavirus transcription, replication and RNA recombination.
4. RNA virus persistence, cross species transmission and virus-host
coevolution.
Our laboratory has studied the mechanism for coronavirus persistence in
vitro. This occurs by virus selection for resistant host cells that down
regulate the expression of the host receptor needed for coronavirus docking
and entry. The emergence of these resistant host cells subsequently selects
for the coevolution of virus variants that recognize new receptors for
docking and entry. Virus variants evolve with expanded host range through
recognition of phylogenetic homologues of the normal coronavirus receptor.
Consequently, we are studying the mechanisms of RNA virus-host cell
coevolution and virus receptor interactions that regulate virus host range
expansion. |
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