Frequent Detection of Human Adenovirus from the Lower Gastrointestinal Tract in Men Who Have Sex with Men

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

doi:10.1371/journal.pone.0011321

Marcel E Curlin, Jared M Baeten + Show 9 more

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https://doi.org/10.1371/journal.pone.0011321

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Abstract

BackgroundThe 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.MethodologyTo 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 −5, −26, −35 and −48 were also assessed.Principal Findings15/20 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, −26 and −48, 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.ConclusionsHAdV 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.

Highlights

Human adenoviruses (HAdVs) are non-enveloped, moderatesized DNA viruses that cause asymptomatic infection and clinical syndromes, including upper respiratory tract infection, conjunctivitis, gastroenteritis, infections of the urinary tract, and serious systemic infections in immunocompromised individuals [1,2]
Subclinical HAdV infection of the GI tract is common among men who have sex with men (MSM) in Peru; the prevalence of HAdV in the enteric tract should be evaluated in other populations
To evaluate whether natural HAdV infections are common in MSM at risk for human immunodeficiency virus (HIV) infection, we examined patterns of HAdV shedding from the genital and lower gastrointestinal tract and tested for preexisting neutralizing antibodies to several proposed HAdV vaccine vectors among HIV-infected MSM undergoing intensive longitudinal mucosal sampling

Summary

Introduction

Human adenoviruses (HAdVs) are non-enveloped, moderatesized DNA viruses that cause asymptomatic infection and clinical syndromes, including upper respiratory tract infection, conjunctivitis, gastroenteritis, infections of the urinary tract, and serious systemic infections in immunocompromised individuals [1,2]. HAdV shedding from the lower GI tract may occur in healthy adults [3,4,5], but is more common in children (where it may represent a primary infection) [6,7,8,9], immunocompromised individuals [2], and persons with HIV infection, those with symptomatic infection and low CD4 counts [3,10,11,12]. In HIV-infected individuals, HAdV shedding has been associated with lower gastrointestinal symptoms such as diarrhea and proctitis in some [3,13,14] but not all studies [5,10,12]. 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

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