Frequent detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men

Marcel Curlin, Meei Li Huang, Xiaoyan Lu, Connie L. Celum, Jorge Sanchez, Stacy Selke, Jared M. Baeten, Richard A. Zuckerman, Dean D. Erdman, Lawrence Corey

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: The association between baseline seropositivity to human adenovirus (HAdV) type 5 and increased HIV acquisition in the Step HIV Vaccine Study has raised questions concerning frequency of acquired and/or persistent Adenovirus infections among adults at high risk of HIV-1 infection. Methodology: To evaluate the frequency and pattern of HAdV shedding from the lower GI tract, we retrospectively tested rectal swabs for HAdVs in a cohort of 20 HSV-2 positive HIV-positive Peruvian men who have sex with men (MSM) undergoing rectal swabbing three times/week for 18 consecutive weeks, in a prospective study of HSV-2 suppression in HIV infection. Viral DNA was extracted and amplified using a sensitive multiplex PCR assay that detects all currently recognized HAdV types. Molecular typing of viruses was performed on selected samples by hexon gene sequencing. Baseline neutralizing antibody titers to HAdVs 25, 226, 235 and 248 were also assessed. Principal Findings: 15/20 individuals had HAdV detected during follow up. The median frequency of HAdV detection was 30% of samples (range 2.0% to 64.7%). HAdV shedding typically occurred on consecutive days in clustered episodes lasting a median of 4 days (range 1 to 9 days) separated by periods without shedding, suggesting frequent new infections or reactivation of latent infections over time. 8 of the 15 shedders had more than one type detected in follow-up. 20 HAdV types from species B, C, and D were identified, including HAdV-5, 226 and 248, HAdV types under development as potential vaccine candidates. 14/20 subjects were seropositive for HAdV-5; 15/20 for HAdV-26; 3/20 for HAdV-35; and 2/20 for HAdV-48. HAdV shedding did not correlate with CD4 count, plasma HIV-1 viral load, or titers to HAdV-5 or HAdV-35. The sole individual with HAdV-5 shedding was HAdV-5 seropositive. Conclusions: HAdV shedding was highly prevalent and diverse, including types presently under consideration as HIV vaccine vectors. Subclinical HAdV infection of the GI tract is common among MSM in Peru; the prevalence of HAdV in the enteric tract should be evaluated in other populations. The association between ongoing recent enteric HAdV and the immune response to recombinant HAdV vaccines should be evaluated.

Original languageEnglish (US)
Article numbere11321
JournalPLoS One
Volume5
Issue number6
DOIs
StatePublished - 2010
Externally publishedYes

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Lower Gastrointestinal Tract
Human Adenoviruses
AIDS Vaccines
Adenoviridae
gastrointestinal system
Adenovirus Vaccines
Human adenovirus C
gender
Viral DNA
Human adenovirus D
Neutralizing Antibodies
Viruses
Assays
Vaccines
Genes
Association reactions
Plasmas
Human adenovirus B
vaccines
viral load

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Frequent detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men. / Curlin, Marcel; Huang, Meei Li; Lu, Xiaoyan; Celum, Connie L.; Sanchez, Jorge; Selke, Stacy; Baeten, Jared M.; Zuckerman, Richard A.; Erdman, Dean D.; Corey, Lawrence.

In: PLoS One, Vol. 5, No. 6, e11321, 2010.

Research output: Contribution to journalArticle

Curlin, M, Huang, ML, Lu, X, Celum, CL, Sanchez, J, Selke, S, Baeten, JM, Zuckerman, RA, Erdman, DD & Corey, L 2010, 'Frequent detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men', PLoS One, vol. 5, no. 6, e11321. https://doi.org/10.1371/journal.pone.0011321
Curlin, Marcel ; Huang, Meei Li ; Lu, Xiaoyan ; Celum, Connie L. ; Sanchez, Jorge ; Selke, Stacy ; Baeten, Jared M. ; Zuckerman, Richard A. ; Erdman, Dean D. ; Corey, Lawrence. / Frequent detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men. In: PLoS One. 2010 ; Vol. 5, No. 6.
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abstract = "Background: The association between baseline seropositivity to human adenovirus (HAdV) type 5 and increased HIV acquisition in the Step HIV Vaccine Study has raised questions concerning frequency of acquired and/or persistent Adenovirus infections among adults at high risk of HIV-1 infection. Methodology: To evaluate the frequency and pattern of HAdV shedding from the lower GI tract, we retrospectively tested rectal swabs for HAdVs in a cohort of 20 HSV-2 positive HIV-positive Peruvian men who have sex with men (MSM) undergoing rectal swabbing three times/week for 18 consecutive weeks, in a prospective study of HSV-2 suppression in HIV infection. Viral DNA was extracted and amplified using a sensitive multiplex PCR assay that detects all currently recognized HAdV types. Molecular typing of viruses was performed on selected samples by hexon gene sequencing. Baseline neutralizing antibody titers to HAdVs 25, 226, 235 and 248 were also assessed. Principal Findings: 15/20 individuals had HAdV detected during follow up. The median frequency of HAdV detection was 30{\%} of samples (range 2.0{\%} to 64.7{\%}). HAdV shedding typically occurred on consecutive days in clustered episodes lasting a median of 4 days (range 1 to 9 days) separated by periods without shedding, suggesting frequent new infections or reactivation of latent infections over time. 8 of the 15 shedders had more than one type detected in follow-up. 20 HAdV types from species B, C, and D were identified, including HAdV-5, 226 and 248, HAdV types under development as potential vaccine candidates. 14/20 subjects were seropositive for HAdV-5; 15/20 for HAdV-26; 3/20 for HAdV-35; and 2/20 for HAdV-48. HAdV shedding did not correlate with CD4 count, plasma HIV-1 viral load, or titers to HAdV-5 or HAdV-35. The sole individual with HAdV-5 shedding was HAdV-5 seropositive. Conclusions: HAdV shedding was highly prevalent and diverse, including types presently under consideration as HIV vaccine vectors. Subclinical HAdV infection of the GI tract is common among MSM in Peru; the prevalence of HAdV in the enteric tract should be evaluated in other populations. The association between ongoing recent enteric HAdV and the immune response to recombinant HAdV vaccines should be evaluated.",
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AU - Huang, Meei Li

AU - Lu, Xiaoyan

AU - Celum, Connie L.

AU - Sanchez, Jorge

AU - Selke, Stacy

AU - Baeten, Jared M.

AU - Zuckerman, Richard A.

AU - Erdman, Dean D.

AU - Corey, Lawrence

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N2 - Background: The association between baseline seropositivity to human adenovirus (HAdV) type 5 and increased HIV acquisition in the Step HIV Vaccine Study has raised questions concerning frequency of acquired and/or persistent Adenovirus infections among adults at high risk of HIV-1 infection. Methodology: To evaluate the frequency and pattern of HAdV shedding from the lower GI tract, we retrospectively tested rectal swabs for HAdVs in a cohort of 20 HSV-2 positive HIV-positive Peruvian men who have sex with men (MSM) undergoing rectal swabbing three times/week for 18 consecutive weeks, in a prospective study of HSV-2 suppression in HIV infection. Viral DNA was extracted and amplified using a sensitive multiplex PCR assay that detects all currently recognized HAdV types. Molecular typing of viruses was performed on selected samples by hexon gene sequencing. Baseline neutralizing antibody titers to HAdVs 25, 226, 235 and 248 were also assessed. Principal Findings: 15/20 individuals had HAdV detected during follow up. The median frequency of HAdV detection was 30% of samples (range 2.0% to 64.7%). HAdV shedding typically occurred on consecutive days in clustered episodes lasting a median of 4 days (range 1 to 9 days) separated by periods without shedding, suggesting frequent new infections or reactivation of latent infections over time. 8 of the 15 shedders had more than one type detected in follow-up. 20 HAdV types from species B, C, and D were identified, including HAdV-5, 226 and 248, HAdV types under development as potential vaccine candidates. 14/20 subjects were seropositive for HAdV-5; 15/20 for HAdV-26; 3/20 for HAdV-35; and 2/20 for HAdV-48. HAdV shedding did not correlate with CD4 count, plasma HIV-1 viral load, or titers to HAdV-5 or HAdV-35. The sole individual with HAdV-5 shedding was HAdV-5 seropositive. Conclusions: HAdV shedding was highly prevalent and diverse, including types presently under consideration as HIV vaccine vectors. Subclinical HAdV infection of the GI tract is common among MSM in Peru; the prevalence of HAdV in the enteric tract should be evaluated in other populations. The association between ongoing recent enteric HAdV and the immune response to recombinant HAdV vaccines should be evaluated.

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