Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression.

[1]  B. Palmer,et al.  HIV-induced alteration in gut microbiota , 2014, Gut microbes.

[2]  C. Duncombe,et al.  Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children adolescents and adults. Recommendations for a public health approach. , 2006 .

[3]  Handan Wand,et al.  Plasma levels of soluble CD14 independently predict mortality in HIV infection. , 2011, The Journal of infectious diseases.

[4]  S. Massart,et al.  Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa , 2010, Proceedings of the National Academy of Sciences.

[5]  J. Doré,et al.  Dysbiosis of fecal microbiota in Crohn's disease patients as revealed by a custom phylogenetic microarray , 2010, Inflammatory bowel diseases.

[6]  R. Hotchkiss,et al.  Reactivation of Multiple Viruses in Patients with Sepsis , 2014, PloS one.

[7]  Connie Celum,et al.  HIV infection: epidemiology, pathogenesis, treatment, and prevention , 2014, The Lancet.

[8]  Jenny Sauk,et al.  Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease , 2015, Cell.

[9]  Susan P. Holmes,et al.  Waste Not , Want Not : Why Rarefying Microbiome Data is Inadmissible . October 1 , 2013 , 2013 .

[10]  J. Brenchley Mucosal immunity in human and simian immunodeficiency lentivirus infections , 2013, Mucosal Immunology.

[11]  F. Bushman,et al.  The human gut virome: inter-individual variation and dynamic response to diet. , 2011, Genome research.

[12]  W. D. de Vos,et al.  Fecal Transplantation Treatment of Antibiotic-Induced, Noninfectious Colitis and Long-Term Microbiota Follow-Up , 2014, Case reports in medicine.

[13]  A. Latorre,et al.  Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals , 2014, Mucosal Immunology.

[14]  R. Bosch,et al.  Body Mass Index and CD4+ T-Lymphocyte Recovery in HIV-Infected Men with Viral Suppression on Antiretroviral Therapy , 2011, HIV clinical trials.

[15]  Rashidul Haque,et al.  Members of the human gut microbiota involved in recovery from Vibrio cholerae infection , 2014, Nature.

[16]  F. Guarner,et al.  Phylogenetic Analysis of Dysbiosis in Ulcerative Colitis During Remission , 2013, Inflammatory bowel diseases.

[17]  D. Kotler,et al.  From wasting to obesity, changes in nutritional concerns in HIV/AIDS. , 2014, Endocrinology and metabolism clinics of North America.

[18]  Jie Dong,et al.  Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery , 2005, Nucleic acids research.

[19]  Lawrence A. David,et al.  Diet rapidly and reproducibly alters the human gut microbiome , 2013, Nature.

[20]  G. Silvestri,et al.  Microbial Translocation in the Pathogenesis of HIV Infection and AIDS , 2013, Clinical Microbiology Reviews.

[21]  Ryan D. Hernandez,et al.  Dysbiosis of the Gut Microbiota Is Associated with HIV Disease Progression and Tryptophan Catabolism , 2013, Science Translational Medicine.

[22]  A. Haase,et al.  Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys. , 2008, The Journal of clinical investigation.

[23]  M. Lyte Microbial Endocrinology in the Microbiome-Gut-Brain Axis: How Bacterial Production and Utilization of Neurochemicals Influence Behavior , 2013, PLoS pathogens.

[24]  Jeffrey N. Martin,et al.  Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy. , 2016, The Journal of infectious diseases.

[25]  Paul M. Ruegger,et al.  HIV Infection is associated with compositional and functional shifts in the rectal mucosal microbiota , 2013, Microbiome.

[26]  S. Tsui,et al.  Detection and identification of plasma bacterial and viral elements in HIV/AIDS patients in comparison to healthy adults. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[27]  H. Virgin,et al.  Kingdom-Agnostic Metagenomics and the Importance of Complete Characterization of Enteric Microbial Communities , 2014, Gastroenterology.

[28]  H. Ullum,et al.  Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus. , 2000, The Journal of infectious diseases.

[29]  G. Pugliese,et al.  Severe Streptococcus pyogenes Infections, United Kingdom, 2003–2004 , 2008, Emerging infectious diseases.

[30]  Matthew J. Gebert,et al.  Alterations in the gut microbiota associated with HIV-1 infection. , 2013, Cell host & microbe.

[31]  Scot E. Dowd,et al.  Exploring the Diversity of Gardnerella vaginalis in the Genitourinary Tract Microbiota of Monogamous Couples Through Subtle Nucleotide Variation , 2011, PloS one.

[32]  Z. Klase,et al.  Dysbiotic Bacteria Translocate in Progressive SIV Infection , 2014, Mucosal Immunology.

[33]  B. Finlay,et al.  Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. , 2007, Cell host & microbe.

[34]  H. Flint,et al.  Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon , 2012, The ISME Journal.

[35]  P. Sansonetti,et al.  Shigella , 2012 .

[36]  L. Hooper,et al.  Resident viruses and their interactions with the immune system , 2013, Nature Immunology.

[37]  N. Neff,et al.  Temporal Response of the Human Virome to Immunosuppression and Antiviral Therapy , 2013, Cell.

[38]  Madison,et al.  Revised surveillance case definition for HIV infection--United States, 2014. , 2014, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[39]  Larissa B. Thackray,et al.  Pathogenic Simian Immunodeficiency Virus Infection Is Associated with Expansion of the Enteric Virome , 2012, Cell.

[40]  D. Richman,et al.  Gut Lactobacillales are associated with higher CD4 and less microbial translocation during HIV infection , 2013, AIDS.

[41]  Herbert W Virgin,et al.  The Virome in Mammalian Physiology and Disease , 2014, Cell.

[42]  J. Brenchley,et al.  Microbial translocation is a cause of systemic immune activation in chronic HIV infection , 2006, Retrovirology.

[43]  R. Bruno,et al.  Transfusion-transmitted virus infection in HIV-1-seropositive patients. , 2000, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[44]  R. Knight,et al.  UniFrac: a New Phylogenetic Method for Comparing Microbial Communities , 2005, Applied and Environmental Microbiology.

[45]  F. Bäckhed,et al.  Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. , 2012, Cell host & microbe.

[46]  P. Gallian,et al.  TT virus infection: prevalence of elevated viraemia and arguments for the immune control of viral load. , 2001, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[47]  H. Guzmán,et al.  Identification of Novel Viruses Using VirusHunter -- an Automated Data Analysis Pipeline , 2013, PloS one.

[48]  M. Fons,et al.  Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent , 2013, PloS one.

[49]  Eric Delwart,et al.  AIDS Alters the Commensal Plasma Virome , 2013, Journal of Virology.

[50]  D. Price,et al.  CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract , 2004, The Journal of experimental medicine.

[51]  A. Keshavarzian,et al.  A Compositional Look at the Human Gastrointestinal Microbiome and Immune Activation Parameters in HIV Infected Subjects , 2014, PLoS pathogens.

[52]  A. Kane,et al.  Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. , 2015, The Journal of infectious diseases.

[53]  H. Virgin,et al.  SIV Infection-Mediated Changes in Gastrointestinal Bacterial Microbiome and Virome Are Associated with Immunodeficiency and Prevented by Vaccination. , 2016, Cell host & microbe.

[54]  A. Phillips,et al.  Ongoing changes in HIV RNA levels during untreated HIV infection: implications for CD4 cell count depletion , 2010, AIDS.

[55]  S. Gianella,et al.  An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia , 2014, Mucosal Immunology.