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

Monaco, Cynthia L.; Gootenberg, David B.; Zhao, Guoyan; Handley, Scott A.; Ghebremichael, Musie; Lim, Efrem S.; Lankowski, Alexander; Baldridge, Megan T.; Wilen, Craig B.; Flagg, Meaghan; Norman, Jason; Keller, Brian C.; Luévano, Jesús M.; Wang, David; Boum, Yap; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.; Siedner, Mark J.; Kwon, Douglas S.; Virgin, Herbert W.

doi:10.1016/j.chom.2016.02.011

Cited by 346 publications

(396 citation statements)

References 53 publications

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“…Of note, correlations between CD4 counts and gut microbial profiles have yielded conflicting results in HIV-infected individuals. Consistent with the above findings in the URT, certain studies have reported a lack of association between CD4 counts and gut microbial composition [55, 56], whereas others have reported associations between CD4 counts and enrichment of certain bacterial taxa [57, 58]. Thus in addition to CD4 counts, other markers of HIV progression should be included in analyses for more robust results.…”

Section: The Bacterial Microbiomesupporting

confidence: 53%

The respiratory microbiome of HIV-infected individuals

Lawani

Morris

2016

Expert Review of Anti-infective Therapy

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Introduction The respiratory tract is constantly exposed to various environmental and endogenous microbes; however, unlike other similar mucosal surfaces, there has been limited investigation of the microbiome of the respiratory tract. Areas Covered In this review, we summarize the current state of knowledge of the bacterial, fungal, and viral respiratory microbiomes during HIV infection and how the microbiome might relate to HIV-associated lung disease. Expert Commentary HIV infection is associated with alterations in the respiratory microbiome. The clinical implications of lung microbial dysbiosis are however currently unknown. Mechanistic studies are needed to establish causality between shifts in the respiratory microbiome and pulmonary complications in HIV-infected individuals.

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Section: The Bacterial Microbiomesupporting

confidence: 53%

The respiratory microbiome of HIV-infected individuals

Lawani

Morris

2016

Expert Review of Anti-infective Therapy

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“…Changes in various components of the microbiome have been observed in association with multiple human diseases (1)(2)(3)(4). Prominent among diseases that are influenced by microorganisms is type 1 diabetes (T1D), a disease involving an autoimmune attack on the insulin-secreting beta cells of the pancreatic islets of Langerhans.…”

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confidence: 99%

“…Changes in intestinal viruses have been observed in patients with inflammatory bowel disease and AIDS (2)(3)(4)12), indicating that changes in the virome can be associated with infectious and inflammatory diseases. In some cases, these changes involve eukaryotic viruses, whereas in other cases, disease-associated changes in bacteriophages have been identified.…”

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confidence: 99%

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Zhao

Vatanen

Droit

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment ofCircoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease.

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“…Using a panenterovirus real-time PCR, we also showed significantly lower C T values in the acute-and chronic-diarrhea groups of animals, supporting generally higher picornavirus RNA loads in diarrheic cases than in the healthy group. The notion that the percentage of sequence read numbers generally reflects the viral load is also supported by studies reporting a correlation between the viral reads and real-time PCR-estimated viral loads (40)(41)(42). A related virome study of SIV-infected rhesus macaques also showed a greater percentage of picornavirus reads (all genotypes combined) in the feces of animals with SIV enteropathy than in a non-SIV-infected control group (15).…”

Section: Discussionmentioning

confidence: 86%

Case-Control Comparison of Enteric Viromes in Captive Rhesus Macaques with Acute or Idiopathic Chronic Diarrhea

Kapusinszky

Ardeshir

Mulvaney

et al. 2017

J Virol

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Diarrhea is the major cause of non-research-associated morbidity and mortality affecting the supply of rhesus macaques and, potentially, their responses to experimental treatments. Idiopathic chronic diarrhea (ICD) in rhesus macaques also resembles ulcerative colitis, one form of human inflammatory bowel disease. To test for viral etiologies, we characterized and compared the fecal viromes from 32 healthy animals, 31 animals with acute diarrhea, and 29 animals with ICD. The overall fractions of eukaryotic viral reads were 0.063% for the healthy group, 0.131% for the acute-diarrhea group, and 0.297% for the chronic-diarrhea group. Eukaryotic viruses belonging to 6 viral families, as well as numerous circular Rep-encoding singlestranded DNA (CRESS DNA) viral genomes, were identified. The most commonly detected sequences were from picornaviruses, making up 59 to 88% of all viral reads, followed by 9 to 17% for CRESS DNA virus sequences. The remaining 5 virus families, Adenoviridae, Astroviridae, Anelloviridae, Picobirnaviridae, and Parvoviridae, collectively made up 1 to 3% of the viral reads, except for parvoviruses, which made up 23% of the viral reads in the healthy group. Detected members of the families Picornaviridae and Parvoviridae were highly diverse, consisting of multiple genera, species, and genotypes. Coinfections with members of up to six viral families were detected. Complete and partial viral genomes were assembled and used to measure the number of matching short sequence reads in feces from the 92 animals in the two clinical and the healthy control groups. Several enterovirus genotypes and CRESS DNA genomes were associated with ICD relative to healthy animals. Conversely, higher read numbers from different parvoviruses were associated with healthy animals. Our study reveals a high level of enteric coinfections with diverse viruses in a captive rhesus macaque colony and identifies several viruses positively or negatively associated with ICD.KEYWORDS enterovirus, sapelovirus, parvovirus, CRESS-DNA, idiopathic diarrhea, rhesus macaques, enteric disease etiology W e compared the enteric viromes of captive rhesus macaques (Macaca mulatta) with acute and idiopathic chronic diarrhea (ICD) to those of healthy animals using a case-control study. The genomes of several known and new viruses were characterized using metagenomics. We showed that some specific enterovirus genotypes and some small circular DNA genomes are associated with chronic idiopathic diarrhea, providing candidates for further testing of their pathogenicity. Other viruses, including some parvoviruses, were found at significantly higher levels in healthy animals.

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

Cited by 346 publications

References 53 publications

The respiratory microbiome of HIV-infected individuals

The respiratory microbiome of HIV-infected individuals

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Case-Control Comparison of Enteric Viromes in Captive Rhesus Macaques with Acute or Idiopathic Chronic Diarrhea

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