Institute of Information Science, Academia Sinica



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Analysis of Human Immunodeficiency Virus Evolution for Identifying Potentially Stable Vaccine Targets

  • LecturerDr. Yaoyu E. Wang (.)
    Host: Dr. HK Tsai
  • Time2011-01-25 (Tue.) 14:00 – 16:00
  • LocationAuditorium 106 at new IIS Building



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.




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.