4.7 Article

Association Between Prolonged Shedding of Zika Virus in Human Semen and Male Reproductive Tract Inflammation

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 226, Issue 7, Pages 1140-1150

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiac329

Keywords

Zika virus; flow cytometry; inflammation; leukocytospermia; male reproductive tract; sexual transmission

Funding

  1. National Institute of Allergy and Infectious Disease, National Institutes of Health [R21AI142504]

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In a study of Zika virus-infected men, prolonged shedding of Zika virus RNA in semen was associated with inflammation in the male reproductive tract, indicated by higher leukocyte counts and inflammatory cytokine levels in semen.
Zika virus (ZIKV) is a mosquito-borne flavivirus that causes congenital defects. Sexual transmission of ZIKV was confirmed in a recent epidemic; however, mechanisms behind ZIKV infection and persistence in the male reproductive tract (MRT) are unknown. Previously, we found that approximately 33% of men with symptomatic ZIKV infections shed ZIKV RNA in semen, and some men shed ZIKV RNA for >3 months. Here, we evaluated the semen of 49 ZIKV-infected men to identify immune factors correlating with long-term ZIKV shedding in semen and ZIKV-infected cell types in semen. We found that prolonged ZIKV RNA shedding in semen was associated with MRT inflammation, indicated by higher leukocyte counts and inflammatory cytokine concentrations in semen of long-term versus short-term shedders. In addition, we found ZIKV RNA in seminal leukocytes and epithelial cells. This study of human semen from ZIKV-infected men provides critical insights into the effects of ZIKV on MRT health. In a large cohort of Zika virus (ZIKV)-infected men, higher leukocyte counts and inflammatory cytokine levels were present in semen from individuals with prolonged seminal shedding of ZIKV than in those with shorter-term ZIKV shedding.

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