Getting to Know the Enemy

(Courtesy of Elena Dukhovlinova)

When Elena Dukhovlinova first heard about the HIV virus in her native Russia in the late 1980s, the reference was to a crisis far away. "It was already kind of perestroika time, and we started getting updated news from other worlds," Dukhovlinova recalls. But HIV did not remain a distant threat; in the years since, HIV/AIDS has become "one of the most complex problems for Russia," the scientist says. Russia's HIV/AIDS problem inspired Dukhovlinova to study molecular epidemiology at the Biomedical Center in St. Petersburg, Russia, where she recently received a Ph.D., studying "the viral population circulating in the city," she says.

"She does lab work, grant-management work, and project coordination, and in this multidisciplinary and multitask environment, she is able to work effectively." --Andrei Kozlov.

This kind of research -- figuring out which of the many HIV strains are affecting local people and how they are transmitted -- is essential for designing an effective vaccine. It also requires a blend of skills that are not easily acquired in Russia: "This field is not recognized," she says. But Dukhovlinova had some unusual opportunities: to join a lab with up-to-date equipment, to attend overseas conferences, to train in the United States, and to work within international collaborations. "I cannot say that there was a special plan in my career," she says. She just followed her interests and ended up with a package of skills that could make a real difference in her country.

Homing in on HIV

More About HIV/AIDS

Read more about the state of the epidemic in Eastern Europe this week in Science magazine's special section on HIV/AIDS.

Like many scientists, Dukhovlinova was inspired to study science by a teacher -- a high school biology teacher named Elena Vorobyova. At Saint-Petersburg State University, Dukhovlinova was ready to choose psychophysiology when a molecular biology course inspired her to revise her plans. This new interest led to a student rotation at the Biomedical Center, which is focused on the development of a vaccine against HIV. She joined the Biomedical Center for a bachelor's degree thesis, working on DNA-vaccine delivery using Salmonella strains.

Andrei Kozlov, the founder of the Biomedical Center and Dukhovlinova's mentor, accepted her in his lab because she proposed an unusual approach to her project, he writes in an e-mail to Science Careers. "Since then she succeeded in almost everything she did." She even shared a patent based on this work, which is "very unusual for the Bachelor student," Kozlov says. Dukhovlinova continued at the center for a master's degree on optimizing vaccine production using Escherichia coli.

After graduating in 2003, Dukhovlinova knew she wanted to continue working with HIV, but she was unsure about the details. While still at the Biomedical Center, she was offered an opportunity to spend a year at Yale University as part of the Training and Research in HIV Prevention in Russia program. At Yale, she attended master's degree lectures in public health -- a degree that didn't exist in Russia. "I learned a lot about all the epidemiology of sexually transmitted diseases ... and general public health topics," she says.

At Yale, she also analyzed the genetic diversity of the HIV viruses infecting injection drug users (IDUs) and men who have sex with men (MSMs) in St. Petersburg. The HIV virus evolves very quickly, so over time infected individuals become hosts to diverse populations of HIV strains. Dukhovlinova tracked transmission chains between infected individuals by looking at the genetic diversity and evolutionary relatedness of their virus populations. She worked under two advisers, a molecular biologist and a prevention specialist. "It was very interesting because it ... was such an interdisciplinary work," she says.

Deciphering transmission

(Courtesy of Elena Dukhovlinova)
Elena Dukhovlinova

Dukhovlinova continued this line of work when she returned to the Biomedical Center, pursuing a Ph.D. Although a great diversity of viral strains develop in patients due to frequent mutations, not all of these strains are transmitted. As a consequence, different viral strains become prevalent in different parts of the world. In Russia, "In the initial phase of the epidemic, we had subtype B strains, which were spread mostly by ... homosexual and heterosexual [routes]," Dukhovlinova explains. In 1998, subtype A strains started appearing in injecting drug users and spreading very fast. Dukhovlinova confirmed this pattern, but she also detected another common mechanism for HIV genetic diversification: In individuals infected with several different HIV viruses, the genetic material gets reshuffled to form brand-new strains.

Dukhovlinova also continued to track transmission chains among HIV-infected patients. Injection drug users (IDUs

) are the main risk group in Russia, but "our studies show that HIV is being spread from this group through the so-called bridging population" -- people who are sexual partners of IDUs but not IDUs themselves -- to the general population by the heterosexual route, Dukhovlinova says. She also found that today transmission occurs mainly among the countries of the former Soviet Union -- a contrast to earlier days, when the MSM population mainly contracted subtype B strains imported from other countries via travel.

Dukhovlinova started pursuing a new line of research when some of the IDUs in her noninfected cohort became acutely infected with HIV. Acute HIV infection corresponds to a phase right after contamination, when the virus replicates rapidly but is temporarily contained by a strong immune response, resulting in often-dismissed flulike symptoms. Dukhovlinova started analyzing the genetic diversity of HIV in these patients in 2008 using single-genome amplification, a sensitive technique that some U.S. collaborators of the Biomedical Center had just reported using.

She joined the collaboration and visited the lab of Ronald Swanstrom at the University of North Carolina (UNC), Chapel Hill, to learn the technique. The resulting work showed that the viral population circulating in newly infected IDUs in St. Petersburg is highly homogeneous, suggesting that in this setting HIV is transmitted mainly by other acutely infected individuals. This contrasts with a study by another group, of a Canadian IDUs cohort, which showed transmission of multiple strains. "We were very surprised by this," Dukhovlinova says.

Applications and limitations

To be most effective, DNA vaccines need to be based on the genes of the viruses present in the target population, so regular genetic diversity monitoring is essential, Dukhovlinova says. Also, if "we prove that people who are acutely infected transmit the virus most, we can use this group as a target group for prevention measures." The Biomedical Center is in the process of getting its first DNA vaccine against HIV into a phase I clinical trial.

Dukhovlinova also applied the knowledge she gained during her stay at Yale to training the next generation of scientists, becoming a teaching assistant for a master's degree program in public health that was being set up at St. Petersburg State as she was returning. She also worked as the coordinator of the Russian side of the international research and education program she attended at Yale. "She does lab work, grant-management work, and project coordination, and in this multidisciplinary and multitask environment, she is able to work effectively," Kozlov says.

Despite her successes, Dukhovlinova regrets the limited impact her work has had on HIV/AIDS in Russia. Partly, it's a policy issue. Many Russian nongovernmental organizations work on the prevention of the HIV epidemic in collaboration with U.S. institutions, but the massive HIV-prevention campaigns the Russian government undertook some years ago seem to have disappeared. Meanwhile, prevention-related studies are routinely ignored, she says. "In our center, we do a lot of research and we publish these data," but "we do not get much attention from the government or from the city government in terms of what to do."

On the human-resources side, too, it's a struggle. The Biomedical Center is one of very few places in Russia where scientists can gain experience in the field. The difficulty of obtaining funding is an obstacle in nearly all research fields in Russia, Kozlov says -- but there's an "obvious lack of interest of the governmental officials [in] this particular topic. Also, the opportunities for individual support of young scientists are quite few." Dukhovlinova has been supported by the various institutional grants that the research programs at the Biomedical Center have attracted -- from two U.S. National Institutes of Health (NIH) institutes, the U.S. Civilian Research & Development Foundation, and the Russian Ministry of Science -- but between grants she has had to work as a translator to support herself.

Looking ahead

Dukhovlinova recently obtained a joint HIV & Drug Use Fellowship from the International AIDS Society and NIH's National Institute on Drug Abuse, which she will use to fund a postdoc with Swanstrom. During her previous stays at UNC, "She was very focused," Swanstrom writes in an e-mail. "Her English is very good and she has a delightful personality, so it was ... an easy choice to accept her ... as a postdoc." Dukhovlinova will continue her current project from UNC, in collaboration with the Biomedical Center. "We need to increase the sample size to be more confident we understand the transmitted virus," Swanstrom says.

When Robert Heimer, one of Dukhovlinova’s Yale mentors, met her when she was a recently graduated master’s student, she was "very desirous of getting more training, improving her English, working on her laboratory skills, but also developing a more well-rounded approach to understanding the problems associated with drug use in HIV disease," he says. The work she has done since demonstrates "that well-trained Russian scientists can do work [that is] equivalent to their American and Westerner counterparts." Her ties to other countries have been "absolutely indispensable because without it, she would be mired in a system that would undervalue her work."

Elisabeth Pain is contributing editor for South Europe.

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