Zika-Induced Male Infertility in Mice Is Potentially Reversible and Preventable by Deoxyribonucleic Acid Immunization

Zika virus (ZIKV) infection has been associated with prolonged viral excretion in human semen and causes testicular atrophy and infertility in 10-week-old immunodeficient mice.

Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 × 105 plaque-forming units at 13 weeks of age. On day 28 postinfection, testes and epididymides were collected in some mice for histological and functional analyses, whereas others were mated with naive female wild-type C57BL/6J.

Although all mice challenged with ZIKV developed viremia, most of them were asymptomatic, showed no weight loss, and survived infection. On day 28 postinfection, none of the unvaccinated, infected mice (9 of 9) exhibited abnormal spermatozoa counts or motility. However, 33% (3 of 9) and 36% (4 of 11) of mated males from this group were infertile, from 2 independent studies. Contrarily, males from the noninfected and the vaccinated, infected groups were all fertile. On days 75 and 207 postinfection, partial recovery of fertility was observed in 66% (2 of 3) of the previously infertile males.

This study reports the effects of ZIKV infection on male fertility in a sublethal, immunodeficient mouse model and the efficacy of GLS-5700 vaccination in preventing male infertility.

The Journal of infectious diseases. 2018 Jul 24 [Epub ahead of print]

Marc-Antoine de La Vega, Jocelyne Piret, Bryan D Griffin, Chantal Rhéaume, Marie-Christine Venable, Julie Carbonneau, Christian Couture, Raquel das Neves Almeida, Roland R Tremblay, Kelly G Magalhães, Young K Park, Christine C Roberts, Joel N Maslow, Niranjan Y Sardesai, J Joseph Kim, Kar Muthumani, David B Weiner, Gary P Kobinger, Guy Boivin

Département de Microbiologie-Infectiologie et d'Immunologie, Université Laval, Québec, Canada., Centre de Recherche en Infectiologie du CHU de Québec - Université Laval, Canada., Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg., Département d'Anatomo-Pathologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada., Laboratory of Immunology and Inflammation, University of Brasilia, Brazil., Unité de Recherche en Reproduction, Santé de la Mère et de l'Enfant, Centre de Recherche du CHU de Québec - Université Laval, Canada., GeneOne Life Science Inc., Seoul, Korea., Inovio Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania., The Wistar Institute, Philadelphia, Pennsylvania.

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