Analysis of Human Immunodeficiency Virus Evolution for Identifying Potentially Stable Vaccine Targets
- 講者Yaoyu E. Wang 博士 (.)
邀請人：蔡懷寬老師 - 時間2011-01-25 (Tue.) 14:00 ~ 16:00
- 地點本所新館106演講廳
摘要
The advancements in high-throughput sequencing technology have
generated an enormous amount of data that enables the
identification of various types of therapeutic targets in
microbes and mammalian cells. Identification of therapeutic
targets against viruses, however, has lagged far behind much
due to the ability of viruses to tolerate a large number of
mutations with minimal fitness cost. Human Immunodeficiency
Virus epitomizes this challenge with its ability to develop
escape mutations against both natural and applied selection
pressure. It is essential to consider HIV evolutionary patterns
in the development of any HIV vaccine to include targets that
remain stable and are resistant to accumulating mutations. Here
we assess the question of target stability for cellular based
HIV vaccine and aim to identify viable target regions through
full HIV genome mutational analysis by examining mutation
patterns across the HIV genome at population level. To this end,
we derived full length viral genomes from hundreds of
genetically well-characterized chronic patients to begin
understand the relationship between human leukocyte allele
(HLA)-associated escape mutations and natural disease
progression. We identified a large number of HLA class I-
associated mutations across the viral genome, reflecting strong
CTL selection pressure shaping genome-wide sequence evolution.
This analysis revealed covariation networks of different
complexity can arise as a response to the deleterious effect of
HLA-associated escape mutations. Due to this requirement of co-
evolving network, we hypothesized and demonstrated that there
exist particular pairs of CTL escape mutations that are uniquely
deleterious to HIV. These data suggest that the combination of
certain HLA class I alleles may enhance the control of HIV
replication due to the inability of HIV to effectively escape
from coordinated responses against structurally interacting
regions of the virus without incurring substantial fitness costs.
These data highlight the importance of CTL based vaccines to
simultaneously direct immune responses against co-evolving sites
that substantially limit the pathways of viral escape.
BIO
Bio:
Dr. Yaoyu Wang received his Ph.D in Bioinformatics from Boston
University in 2006 on devising computational methods for
selecting stable therapeutic targets from highly mutable
retroviruses. After graduation he joined the Ragon Institute of
MGH, MIT and Harvard to study HIV evolution under immune
pressures to identify viral regions suitable for anti-viral
vaccine design by performing population sequencing of HIV genome.
Dr. Wang joined the Center for Computational Cancer Biology at
Dana-Farber Cancer Institute in fall of 2009 to provide
education and research consultation services in biomedical data
analysis. Since then he has collaborated with researchers
across the Boston area to study different diseases using high
throughput technologies.