Abstract

BackgroundHuman herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication (“shedding”) at mucosal sites, especially the oropharynx. Patterns of HHV-8 shedding are not well understood, and require elucidation to better predict risk of HHV-8 related malignancies in those infected. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV-8 seropositive persons.MethodsWe quantified HHV-8 oral shedding using PCR among HHV-8 seropositive persons who collected at least 14 days of oral swabs in 22 studies on 3 continents. We excluded persons taking antivirals during sampling or any prior use of antiretrovirals in those who were HIV-infected.Results248 participants were enrolled from the US, Peru, Cameroon, Uganda, and Kenya; 61 % were men, 58 % were HIV seropositive, and 16 % had KS. Overall, 3,123 of 10,557 samples (29.6 %) had HHV-8 detected. Quantity of virus shed was highly correlated with shedding rate, (ρ = 0.72, p < 0.0001). HHV-8 was detected in ≥1 sample in 55 % of participants with a median of 7 % of days in the US and Kenya, 0 % in Uganda and Peru, and 18 % in Cameroon. Median episode duration was three days, and episodes with high median quantity lasted longer (42 vs 3 days, p < 0.0001). In persons with multiple observations over time, 66 % of shedding rate variance was attributable to differences between individuals.ConclusionsIn HHV-8 infected individuals from diverse settings, oral mucosal shedding rate, quantity, and duration were correlated; individual shedding was highly variable. Studies are needed to determine factors accounting for between-person variation and the relationship of HHV-8 shedding to development of associated diseases.

Highlights

  • Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication (“shedding”) at mucosal sites, especially the oropharynx

  • While in most people HHV-8 is asymptomatic, HHV-8 replication is considered to be integral to the development and maintenance of Kaposi sarcoma (KS)

  • HSV-2 reactivation is characterized by shorter episodes with 20 % lasting >9 days [18], whereas we found longer episodes of HHV-8 shedding, with 40 % ongoing at 20 days

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Summary

Introduction

Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication (“shedding”) at mucosal sites, especially the oropharynx. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV-8 seropositive persons. Human herpesvirus-8 (HHV-8), known as Kaposi sarcoma-associated herpesvirus (KSHV), establishes lifelong latent infection, punctuated with periods of lytic replication at mucosal sites (“shedding”) [1]. The patterns of HHV8 shedding, such as duration of shedding episodes, interval between episodes, and variability between persons have not yet been characterized. Due to the heterogeneity of cohort composition, we describe shedding characteristics and patterns across all persons, avoiding prediction of shedding by geographic, demographic or clinical covariates. We assembled diverse cohorts of HHV-8 infected individuals to describe patterns of HHV-8 oral mucosal shedding including rate, quantity, duration, and within- versus between-person variability over time

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