Scientists at Johns Hopkins and in India report they have sequenced the complete genome of a form of HIV, the AIDS virus, from that country for the first time. The work has revealed unexpected variation in genes for one key part of the virus, prompting the researchers to suggest that currently favored approaches to vaccine development may not work.
The achievement, reported in this month's Journal of Virology, also suggests that different forms of HIV in India, unlike the single U.S. virus type, may be combining in a way that will further complicate vaccine development.
Researchers know that the genetic makeup of the virus varies with geography; they've catalogued 10 possible different HIV subtypes, lettered A to J. The United States subtype, for example, is largely subtype B. "India's strains are primarily subtype C, a variety also dominant in Africa and Southeast Asia," says Hopkins virologist Stuart C. Ray, M.D., who directed the U.S. arm of the study. "But we were curious to see if India's subtype C differed in important ways from the others." Knowing a subtype's makeup is an important step on the road to a vaccine, he says.
The research team drew blood samples from six newly infected Indian volunteers: two had received contaminated transfusions and four were clients of a sexually transmitted disease clinic in western India. The samples reflect HIV variation in that country, the researchers say. The PCR technique to amplify the viral genes and their resulting analysis took place at Hopkins.
The scientists found that, while the virus has much in common with subtype C samples worldwide, the genes coding for proteins in the outer "envelope" of the virus -- the target of most of the trial anti-viral vaccines to date -- vary significantly from the subtype B strains that form the backbone of vaccines currently in international trials. "It means we could expect problems with any vaccine based solely on envelope proteins," says Ray. "We should probably look to other places in the virus for a vaccine ."
A second result also may signal problems. "One of the six patients had a virus that was a mosaic, or blend, of subtype C and subtype A," says Ray. "In Thailand and Brazil, unlike the United States, mosaics are the major players in the epidemic, and we believe mosaics may have a survival advantage over single subtype strains. Studies also suggest it's harder to make a vaccine against cross-strains. We're concerned that the A/C combination could become common and that single-strain vaccines won't work."
Literally thousands of people are newly infected with HIV each day in India, making the country the world's number one hot spot for the disease. Part of India is included in the Golden Triangle, an intense area of drug use and trafficking, and "that's an important part of the problem," says Ray. "Even more, however, comes from heterosexual transmission.
"Countries like India don't have money to pay for expensive drug treatments, so our best hope is a vaccine," he adds, "and we need to find the proper principle to develop one quickly."
Other scientists on the Hopkins research team were Robert C. Bollinger, M.D., and Nicole G. Novak, M.S. Kavita S. Lole and Deepak Gadkari of the National Institute of Virology, Pune, India; Smita S. Kulkarini and Ramesh S. Paranjape of the National AIDS Research Institute, Pune, India were also on the study team, as was Haynes Sheppard of the California Department of Health Services at Berkeley.
Research was funded by NIH grants and support from the government of India.
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