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Tips from the journals of the American Society for Microbiology

American Society for Microbiology

How Flu Virus Spreads To College Community: Major Implications for Control

Many different strains of the H1N1 influenza virus were represented among 57 students at the University of California, San Diego (UCSD) who were infected during the epidemic in the fall of 2009, according to a paper in the July Journal of Virology. The findings have major implications in the controversy over how best to reduce the virus' spread.

The investigators had planned the study in the spring of 2009, after a new strain of H1N1 was identified in San Diego, and spread rapidly around the world, says coauthor Robert T. Schooley of UCSD. "We reasoned that the epidemic would resume in the fall and that the college-age population would be particularly at risk since people under age 50 had lower levels of immunity to the new strain."

The investigators theorized that if they found a single strain, or a very limited number of strains, that would indicate that spread between the campus and the general community might be reduced by quarantines, says Schooley. "But if multiple strains of virus were circulating, that would suggest multiple introductions of the virus into the college community, that would be unlikely to be interdicted by efforts at quarantine." So they set up a prospective study to collect viral isolates from students presenting with influenza-like symptoms "when the epidemic returned in the fall," says Schooley.

The investigators identified at least 21, and possibly as many as 33, different viral strains from among the 57 students. Those results suggested that the virus had been introduced repeatedly into the college population within a very short period of time, suggesting that "quarantine efforts in the college population would have a minimal effect on limiting spread of the newly emerging strain," says Schooley. More generally, he says that quarantine, class cancellation, distribution of respiratory isolation equipment, and other isolation measures "within susceptible socially active populations such as those found on college campuses is unlikely to be effective, and that other approaches such as vaccination, focused use of antiviral drugs among those with underlying illnesses predisposing to more severe illness should be emphasized instead."

(E.C. Holmes, E. Ghedin, R.A. Halpin, et al. Extensive geographical mixing of 2009 human H1N1 influenza A virus in a single university community. J. Virol. 85:6923-6929.)

Research Illuminating Long-Term Non-Progression Suggests Novel Vaccination Strategy for HIV

A major problem researchers have faced in attempting to develop a vaccine for HIV is that the virus mutates incredibly quickly, which means that its antigens--the target molecules of a vaccine--are moving targets. A comparison of individuals who are able to control HIV without antiretroviral medication with those who are unable to do so suggests that a novel approach to vaccination might work around this problem. The research is published in the July Journal of Virology.

Human DNA contains so-called human endogenous retroviruses (HERVs), which are remnants of ancient retroviruses--genetic fossils--that under normal circumstances sit silently, and always genetically stably, within human DNA. In earlier work, a team of researchers led by Douglas Nixon of the University of California, San Francisco, showed that infection with HIV activates HERVs that lie inside HIV-infected cells in some individuals (but not those in non-infected cells), by interfering with regulatory compounds that normally prevent expression of these HERVs. The activated HERVs produce proteins that attract immune system T cells to the HIV-infected cells, targeting them for destruction. The researchers also showed that the greater T cell response, the lower an individual's viral load.

In the new research, Devi SenGupta of the University of California, San Francisco et al. extended these findings to include individuals who have long-term chronic HIV-1 infection. They compared the responses of a tiny subset of individuals who are unique in their ability to suppress the virus indefinitely without the aid of combination therapy to those of patients on highly active antiretroviral therapy (HAART), virologic noncontrollers, immunologic progressors, and uninfected controls. A strong anti-HERV response corresponded to a lower viral load, and a higher CD4+ T cell count. "Interestingly, controllers who lack HLA alleles [critical immune system components] that are associated with protection from HIV-1 disease progression... constituted a large proportion of the subjects with the strongest HERV responses, suggesting that there may be an alternative mechanism of HIV control (such as HERV-specific cytotoxic T cells) in these controllers," the researchers write.

The findings suggest that a vaccination targeting proteins produced by the HERV genes could help the immune system keep HIV in check, says SenGupta. "Our research helps lay the groundwork for developing a new therapeutic or preventive vaccine against HIV. If this leads to a new anti-HIV therapy, millions of lives could be improved all over the world."

(D. SenGupta, R. Tandon, R.G.S. Vieira et al. Strong human endogenous retrovirus-specific T cell responses are associated with control of HIV-1 in chronic infection. J. Virol. 85:6977-5985.)

"ID1" Protein Boosts Lung Cancer In Smokers, Non-Smokers; Potential Anti-Oncogenic Target

Lung cancer is strongly correlated with smoking, and most lung cancer patients are current or former smokers. But it is not rare in nonsmokers. Now, a team of researchers from the H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, shows that a protein called ID1 is a key player in lung cancer in both smokers and nonsmokers. The research is published in the July issue of the journal Molecular and Cellular Biology.

The investigators were aware that while nicotine does not cause cancer, earlier studies, including their own, had suggested that it might promote growth and metastasis of cancers that had already formed. They exposed cultured cells to nicotine, after which these cells expressed increased levels of a protein called ID1.

"That protein was the first link between lung cancer in smokers and nonsmokers. In non-smokers, who are not exposed to copious nicotine, its expression is induced by a growth promoting protein called epidermal growth factor, which is known to be involved in cancers in non-smokers," says corresponding author Srikumar Chellappan.

The researchers then connected all this to another protein, Src, which was known to be altered in cancers, and in this altered form to promote tumor growth. "Our studies showed that inhibiting Src prevented the induction of ID1," says Chellappan. "Further, removing ID1 protein from cancer cells prevented their growth, as well as their ability to migrate or invade, which are the early steps of metastasis." They removed ID1 from the cancer cells through the use of small-interfering RNAs, which can be designed to block expression of particular proteins.

"Our studies thus show that ID1 might mediate the tumor promoting properties of nicotine, and also facilitate the growth of tumors in response to epidermal growth factor," says Chellappan. "These observations raise the possibility that targeting ID1 might be a viable strategy for combating lung cancer."

(S. Pillai, W. Rizwani, X. Li, B. Rawal, S. Nair, M.J. Schell, G. Bepler, E. Haura, D. Coppola, and S. Chellappan, 2011. ID1 facilitates the growth and metastasis of non-small cell lung cancer in response to nicotinic acetylcholine receptor and epidermal growth factor receptor signaling. Mol. Cell. Bio. 31:3052-3067.)

Antibiotic Disrupts Termite Microflora, Reducing Fertility, Longevity

The microbial flora of the termite gut are necessary both for cellulose digestion and normal reproduction, and feeding the insects antibiotics can interfere in these processes, according to a paper in the July issue of the journal Applied and Environmental Microbiology.

"New and effective technologies for the control of social insect pests may be devised as a result of this work," says corresponding author Rebeca B. Rosengaus of Northeastern University, Boston, MA.

In this study, the researchers fed wood and the antibiotic rifampin to an experimental group of termite queens and kings, while feeding wood and water to a control group. The antibiotic treatment permanently reduced the diversity of the gut microbiota. Although antibiotic-fed queens and kings suffer higher mortality than their control counterparts, the authors do not believe the mortality was due to malnutrition or starvation. Surviving antibiotic-fed queens and kings had reduced rates of oviposition, which resulted in delayed colony growth, and reduced colony fitness. "These results point to the potential for using antibiotics to control termites and/or other insect pests, while reducing the need to attack them with toxic pesticides," says Rosengaus.

In the paper, the researchers speculate that rifampin reduces fertility and longevity by disrupting mutualistic bacterial partnerships within the hosts. "Given the long coevolutionary history between the gut symbionts and termites, it is likely that these social insects accrue additional benefits from their microbiota that are unrelated to cellulolytic activity," they write, noting that in other insects, gut symbionts are known to help in "...detoxification, mediation of disease resistance and immune function, production of volatile compounds that are coopted to function as aggregation or kin recognition pheromones and defensive secretions, and performance of atmospheric nitrogen fixation."

Besides the possibility that the research will lead to methods for curbing termites and other social insect pests, it may illuminate the co-evolutionary history of an ancient relationship, says Rosengaus. "These host-microbial interactions likely influence the evolution of multiple life history traits of hosts, including their longevity, behavior, reproductive biology, immunity, and perhaps even the evolution and maintenance of their sociality," she says.

The work might even have relevance to human physiology, says Rosengaus. Hundreds of species of microbe inhabit the human gut, and researchers are beginning to show how the compounds these microbes produce influence our physiology. "Understanding the possible impacts that these microbes have on the physiology of insects--a more tractable animal model--we can make inferences about the multiple roles that human gut microbes have on our physiology," says Rosengaus.

(R.B. Rosengaus, C.N. Zecher, K.F. Schultheis, R.M. Brucker, and S.R. Bordenstein, 2011. Disruption of the termite gut microbiota and its prolongued consequences for fitness. Appl. Environ. Micriobiol. 77:4303-4312.)


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