Influenza papers published!
18/11/11 13:26
I’m excited to report that two new papers have recently been published describing my lab’s work on influenza immunity and pathogenesis. Both of these studies were conducted in collaboration with my UW colleague Yoshi Kawaoka.
The first, led by my lab, shows that cross-reactive T cell responses play a role in rapid clearance of 2009 H1N1 influenza viruses from the upper and lower respiratory tract in nonhuman primates. This observation is important because it establishes a role for T cells in protective immunity against influenza in a humanlike model system. Such “heterosubtypic” T cell responses were known to protect mice against divergent influenza viruses, but scientists have disagreed on the significance of heterosubtypic immunity to influenza in humans.
Our results showed that monkeys “primed” to make flu-specific T cell responses by prior infection with a seasonal virus were able to clear a challenge with the 2009 H1N1 pandemic virus more rapidly than naive animals. This enhanced clearance was associated with rapid recall of memory T cell responses and occurred before the emergence of neutralizing antibodies specific for the 2009 H1N1 virus.
These results suggest that cross-reactive T cells could play a similar role in humans, allowing for the rapid containment of infection even in the absence of neutralizing antibodies. Since current influenza vaccines are designed specifically to induce antibodies, we speculate that adding vaccine components designed to elicit T cells could would enhance influenza vaccine efficacy, particularly against emerging viruses. These results were published in PLoS Pathogens.
The second study, led by Yoshi’s group, investigates the impact of a mutation in the hemagglutinin (HA) protein of the 2009 H1N1 influenza virus on virus tropism and disease severity. This was a major collaborative study in which my group contributed expertise in nonhuman primate virology. It was based on the observation that pandemic viruses isolated from some patients with unusually severe (sometimes fatal) disease had a particular mutation in HA, frequently referred to as D222G or D225G. (The numbers differ depending on which virus strain is used for reference, but they refer to the same mutation.)
Together, our experiments showed that the D222G mutation altered the tropism of the virus, allowing it to bind to both human- and avian-type receptors. As a result, the mutant virus binds to different types of cells in the respiratory tract than the wild type virus does. Specifically, the mutant virus can infect Type II pneumocytes. These cells are not directly involved in gas exchange in the lungs, but they are the progenitors of gas-exchanging Type I pneumocytes. At least one strain of D222G virus caused much more severe disease in infected monkeys than wild type viruses did, suggesting that the D222G mutation can indeed increase influenza virus virulence. We speculate that viral destruction of Type II pneumocytes may limit the lung’s ability to repair damage, which could explain the increased severity of disease seen in monkeys and humans infected with D222G variant viruses. This study is now in press at the Journal of Virology.
The first, led by my lab, shows that cross-reactive T cell responses play a role in rapid clearance of 2009 H1N1 influenza viruses from the upper and lower respiratory tract in nonhuman primates. This observation is important because it establishes a role for T cells in protective immunity against influenza in a humanlike model system. Such “heterosubtypic” T cell responses were known to protect mice against divergent influenza viruses, but scientists have disagreed on the significance of heterosubtypic immunity to influenza in humans.
Our results showed that monkeys “primed” to make flu-specific T cell responses by prior infection with a seasonal virus were able to clear a challenge with the 2009 H1N1 pandemic virus more rapidly than naive animals. This enhanced clearance was associated with rapid recall of memory T cell responses and occurred before the emergence of neutralizing antibodies specific for the 2009 H1N1 virus.
These results suggest that cross-reactive T cells could play a similar role in humans, allowing for the rapid containment of infection even in the absence of neutralizing antibodies. Since current influenza vaccines are designed specifically to induce antibodies, we speculate that adding vaccine components designed to elicit T cells could would enhance influenza vaccine efficacy, particularly against emerging viruses. These results were published in PLoS Pathogens.
The second study, led by Yoshi’s group, investigates the impact of a mutation in the hemagglutinin (HA) protein of the 2009 H1N1 influenza virus on virus tropism and disease severity. This was a major collaborative study in which my group contributed expertise in nonhuman primate virology. It was based on the observation that pandemic viruses isolated from some patients with unusually severe (sometimes fatal) disease had a particular mutation in HA, frequently referred to as D222G or D225G. (The numbers differ depending on which virus strain is used for reference, but they refer to the same mutation.)
Together, our experiments showed that the D222G mutation altered the tropism of the virus, allowing it to bind to both human- and avian-type receptors. As a result, the mutant virus binds to different types of cells in the respiratory tract than the wild type virus does. Specifically, the mutant virus can infect Type II pneumocytes. These cells are not directly involved in gas exchange in the lungs, but they are the progenitors of gas-exchanging Type I pneumocytes. At least one strain of D222G virus caused much more severe disease in infected monkeys than wild type viruses did, suggesting that the D222G mutation can indeed increase influenza virus virulence. We speculate that viral destruction of Type II pneumocytes may limit the lung’s ability to repair damage, which could explain the increased severity of disease seen in monkeys and humans infected with D222G variant viruses. This study is now in press at the Journal of Virology.
Virus discovery published!
25/04/11 18:19
Lately I’ve been working with my UW colleagues Tony Goldberg and David O’Connor on a really cool project aimed at understanding how viruses are transmitted among species and the processes by which novel viruses might emerge in human populations. In his studies of viral ecology, Tony was able to collect blood samples from wild monkeys in Kibale National Park in Uganda.
Here in our labs at UW, we used a direct pyrosequencing technique to determine what RNA viruses might be present in the blood of one of these animals, a red colobus monkey. Much to our surprise, we found two novel, divergent simian hemorrhagic fever viruses (SHFVs). These viruses do not infect people, and have previously only been observed in captive monkeys.
What were these two viruses doing in a healthy, free living, wild monkey?
A paper describing our study has just been published. Check it out here.
Here in our labs at UW, we used a direct pyrosequencing technique to determine what RNA viruses might be present in the blood of one of these animals, a red colobus monkey. Much to our surprise, we found two novel, divergent simian hemorrhagic fever viruses (SHFVs). These viruses do not infect people, and have previously only been observed in captive monkeys.
What were these two viruses doing in a healthy, free living, wild monkey?
A paper describing our study has just been published. Check it out here.
Happy New Year!
06/01/11 18:22
Another semester has passed by. They really do seem to go more quickly each year. I’m happy to say that this year’s installment of HIV: Sex, Science and Society went very well. Students asked smart, interesting questions, and hopefully enjoyed the course. We’ve heard from several students who said they really enjoyed the class, and we’ve also had some great suggestions for future improvements. Thanks to everyone who participated in this year’s course!
It’s also been a very busy time in the lab. I’m proud to say that the first last-author publication to come from my group has just appeared in the Journal of Virology. You can find the abstract at PubMed here. We’ve also been working on some other exciting projects, which I hope will be published soon. Stay tuned!
It’s also been a very busy time in the lab. I’m proud to say that the first last-author publication to come from my group has just appeared in the Journal of Virology. You can find the abstract at PubMed here. We’ve also been working on some other exciting projects, which I hope will be published soon. Stay tuned!
More meetings
24/08/10 16:44
Wow, it’s been a really busy summer. There’s been a lot to do in the lab, with influenza and AIDS research projects in full swing. I’m also about to head to Hong Kong to present some of our work at the Options for the Control of Influenza conference -- check it out on September 4th if you’re in town.
With the beginning of the fall semester, we will be starting a new installment of our course on HIV for undergrads, HIV: Sex, Science and Society (Path/PBS 210). We’ve once again updated the course materials, in part to reflect the recently reported results from the groundbreaking CAPRISA trial of an antiretroviral gel that affords women some level of protection against acquiring HIV infection. I’m excited to be teaching again this semester. See you once I get back from Hong Kong!
With the beginning of the fall semester, we will be starting a new installment of our course on HIV for undergrads, HIV: Sex, Science and Society (Path/PBS 210). We’ve once again updated the course materials, in part to reflect the recently reported results from the groundbreaking CAPRISA trial of an antiretroviral gel that affords women some level of protection against acquiring HIV infection. I’m excited to be teaching again this semester. See you once I get back from Hong Kong!
Traveling, speaking, writing...
12/03/10 10:20
It’s been a busy month for us, both in the lab and elsewhere. Last week I visited Johns Hopkins University in Baltimore, where I gave a talk on our influenza research for their Department of Molecular and Comparative Pathobiology. I had an interesting and rewarding visit. Many thanks to Joe Mankowski for the invitation!
Today I’ll be speaking at the Student American Veterinary Medicine Association (SAVMA) Symposium at the Monona Terrace here in Madison. I’ll discuss the important role of veterinary medicine in global health, and how research vets have made critical contributions to our understanding of AIDS. I’m excited to talk to a large and diverse gathering of veterinary students.
I’m also happy to say that a study I conducted with Eva Rakasz and colleagues at the Wisconsin National Primate Research Center has just been published online by the Journal of Virology.
Today I’ll be speaking at the Student American Veterinary Medicine Association (SAVMA) Symposium at the Monona Terrace here in Madison. I’ll discuss the important role of veterinary medicine in global health, and how research vets have made critical contributions to our understanding of AIDS. I’m excited to talk to a large and diverse gathering of veterinary students.
I’m also happy to say that a study I conducted with Eva Rakasz and colleagues at the Wisconsin National Primate Research Center has just been published online by the Journal of Virology.