08:31am Saturday 18 January 2020

HIV may leave gut vulnerable to infections


“What we learned from this study will help us better understand the progression of AIDS in humans,” says senior author Herbert W. “Skip” Virgin IV, MD, PhD, the Edward Mallinckrodt Professor and head of Pathology and Immunology. “Advanced AIDS patients often develop gastrointestinal disease, and now we have a model for learning why that happens.”

The research, published in Cell, was conducted in association with Harvard Medical School, the National Institute of Allergy and Infectious Diseases, Tulane University, Duke University, the Ragon Institute, the Massachusetts Institute of Technology and other affiliated institutions.

The primates are housed at the National Institutes of Health, the New England Primate Research Center of Harvard Medical School and the Tulane University National Primate Research Center. Some of them were given simian immunodeficiency virus (SIV), which is closely related to human immunodeficiency virus (HIV).

The scientists analyzed genetic material from fecal samples of primates, including macaques and African green monkeys. They identified 32 previously undescribed intestinal viruses in primates infected with forms of SIV that caused an AIDS-like illness. Only a small subset of these viruses were found in control group primates, which had been infected with non-pathogenic forms of SIV or had not been infected with SIV.

Studies have suggested that a significant portion of the harm that AIDS inflicts on the human immune system takes place in the intestinal tract, where the body’s defenses carefully balance attacks against hostile invaders with tight regulation of microbes that aid digestion.

Maintaining this balance draws many immune cells to the gut, including the cells targeted by HIV. Scientists have speculated that the toll HIV takes on these cells could make it easier for disease-causing microbes to infect the gut.

“An earlier investigation of how SIV affects microorganisms in the gut was limited to bacteria and didn’t find any significant changes,” says co-first author Scott Handley, PhD, research instructor in pathology and immunology. “We now have technology that lets us assess changes in the viral community in the digestive tract, and we found significant and possibly harmful changes.”

A number of the viruses that the researchers identified in primates with SIV are picornaviruses, a broad group of viruses that includes poliovirus as well as viruses that cause hand, foot and mouth disease or colds in humans. They also found genetic material from:

  • adenoviruses, which cause respiratory and gastrointestinal diseases
  • parvoviruses, which cause human disease and are common in animals
  • caliciviruses, a group that includes the viruses that cause outbreaks of diarrhea on cruise ships and a significant amount of disease worldwide

“Some of the viruses we identified have never been observed before,” says co-first author Guoyan Zhao, PhD, research assistant professor of pathology and immunology. “Some may even be members of a new genus, a category for classifying life forms.”

Genetic material from some of the viruses the scientists identified also was present in the bloodstream, suggesting that the viruses had crossed into the circulatory system from the gut.

“Moving forward, we will study the properties of these novel viruses to determine what they, or other viruses, may be doing to harm the digestive systems of AIDS patients and to advance the progression of disease,” says co-first author Larissa Thackray, PhD, research assistant professor of pathology and immunology.

Handley SA, Thackray LB, Zhao G, Presti R, Miller AD, Droit L, Abbink P, Maxfield LF, Kambal A, Duan E, Stanley K, Kramer J, Macri SC, Permar SR, Schmitz JE, Mansfield K, Brenchley JM, Vazey RS, Stappenbeck TS, Wang D, Barouch DH, Virgin HW. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell, October 12, 2012.

This research was supported by the National Center for Research Resources (U54 AI057160-08); the Office of Research Infrastructure Programs (OD11170-02); Crohn’s and Colitis Foundation Grant 3132; and other NIH grants (AI066305, AI066924, AI078526, AI095985, AI65335, and 8P51OD011103-5).

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

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