Featured Research

from universities, journals, and other organizations

Deeper view of HIV reveals impact of early mutations

Date:
March 8, 2012
Source:
Massachusetts General Hospital
Summary:
Mutations in HIV that develop during the first few weeks of infection may play a critical role in undermining a successful early immune response, a finding that reveals the importance of vaccines targeting regions of the virus that are less likely to mutate.

Mutations in HIV that develop during the first few weeks of infection may play a critical role in undermining a successful early immune response, a finding that reveals the importance of vaccines targeting regions of the virus that are less likely to mutate. A new study in the journal PLoS Pathogens, led by researchers at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard and the Broad Institute of MIT and Harvard, applied the same next-generation technologies that have revolutionized sequencing of the human genome to study how HIV adapts within the first few weeks after infection.

Related Articles


Ragon and Broad investigators applied an approach called pyrosequencing that allows the simultaneous sequencing of hundreds of viral variants within an individual over the course of infection. These data provided a substantially deeper and more sensitive view of the complexity of mutant strains circulating in a patient following HIV infection and how each of those strains evolves over time. Combining these genetic data with detailed immunological analyses enabled a comprehensive evaluation of viral-host interactions during the critical acute phase of HIV infection.

The study revealed that the majority of early, low-frequency mutations developing during the first few weeks after infection represent rapid adaptations to avoid the response of CD8 'killer' T cells, which play a key role in recognizing and eliminating HIV-infected cells. "These data reveal the ability of HIV to rapidly avoid front-line immune responses attempting to contain the infection," says Todd Allen, PhD, senior author of the study and a Ragon Institute faculty member.

More importantly, Allen notes, their study revealed that rapid viral escape from a few dominant immune responses coincided with the inability of individual patients to maintain early control of HIV. "The ability to sensitively assess early virus evolution across the entire HIV genome revealed that limiting the ability of HIV to become resistant to the earliest immune responses may be a critical component of a successful vaccine," he says. "Therefore, the key to controlling a highly variable pathogen such as HIV may lie in a vaccine's ability to redirect immune responses towards more critical, highly conserved regions of the virus that are unable to successfully mutate."

An important component of the study was development of novel bioinformatics tools to handle the enormous and highly diverse sequence dataset and to assemble the thousands of sequencing reads into complete HIV genomes for analysis and detection of genetic mutations. While next-generation sequencing approaches have helped transform the sequencing of mammalian genomes, the high degree of sequence diversity within and between HIV strains has hindered the routine application of those powerful sequencing approaches to highly variable pathogens such as HIV. In the current study the researchers were able to apply their approach to successfully sequence the entire HIV genome from dozens of infected individuals.

"The genomic and computational tools developed as part of this study allow researchers to interrogate the complete HIV genome and to identify genetic variants of the virus with unprecedented resolution, allowing us to obtain a novel map of how the virus is changing during the course of an infection." says Matthew Henn, PhD, the lead author of the study and director of Viral Genomics at the Broad Institute.

Efforts to develop an effective vaccine against HIV have been thwarted in large part because of the virus's ability to rapidly mutate and avoid host immune responses. However, notes Allen -- an associate professor of Medicine at Harvard Medical School -- "HIV is not able to mutate at will. Some of these mutations substantially cripple the virus' ability to replicate, which appears to be critical to enabling a few individuals to uniquely control HIV without the need for therapy."

Understanding more precisely how HIV evolves in an individual and how mutations correlate with the ability to control HIV may provide critical insight into the design of more effective vaccines to contain and possibly prevent infection altogether. Efforts are underway at the Ragon Institute to harness these findings to develop and test novel vaccine approaches against HIV that limit its ability to mutate and escape immune control.

The study was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health; the Bill and Melinda Gates Foundation, and the Department of Health and Human Services.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Matthew R. Henn, Christian L. Boutwell, Patrick Charlebois, Niall J. Lennon, Karen A. Power, Alexander R. Macalalad, Aaron M. Berlin, Christine M. Malboeuf, Elizabeth M. Ryan, Sante Gnerre, Michael C. Zody, Rachel L. Erlich, Lisa M. Green, Andrew Berical, Yaoyu Wang, Monica Casali, Hendrik Streeck, Allyson K. Bloom, Tim Dudek, Damien Tully, Ruchi Newman, Karen L. Axten, Adrianne D. Gladden, Laura Battis, Michael Kemper, Qiandong Zeng, Terrance P. Shea, Sharvari Gujja, Carmen Zedlack, Olivier Gasser, Christian Brander, Christoph Hess, Huldrych F. Günthard, Zabrina L. Brumme, Chanson J. Brumme, Suzane Bazner, Jenna Rychert, Jake P. Tinsley, Ken H. Mayer, Eric Rosenberg, Florencia Pereyra, Joshua Z. Levin, Sarah K. Young, Heiko Jessen, Marcus Altfeld, Bruce W. Birren, Bruce D. Walker, Todd M. Allen. Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection. PLoS Pathogens, 2012; 8 (3): e1002529 DOI: 10.1371/journal.ppat.1002529

Cite This Page:

Massachusetts General Hospital. "Deeper view of HIV reveals impact of early mutations." ScienceDaily. ScienceDaily, 8 March 2012. <www.sciencedaily.com/releases/2012/03/120308174809.htm>.
Massachusetts General Hospital. (2012, March 8). Deeper view of HIV reveals impact of early mutations. ScienceDaily. Retrieved October 26, 2014 from www.sciencedaily.com/releases/2012/03/120308174809.htm
Massachusetts General Hospital. "Deeper view of HIV reveals impact of early mutations." ScienceDaily. www.sciencedaily.com/releases/2012/03/120308174809.htm (accessed October 26, 2014).

Share This



More Health & Medicine News

Sunday, October 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
Toxin-Packed Stem Cells Used To Kill Cancer

Toxin-Packed Stem Cells Used To Kill Cancer

Newsy (Oct. 25, 2014) — A Harvard University Research Team created genetically engineered stem cells that are able to kill cancer cells, while leaving other cells unharmed. Video provided by Newsy
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins