Zika virus in semen and spermatozoa

Mansuy, Jean Michel; Suberbielle, Elsa; Chapuy‐Regaud, Sabine; Mengelle, Catherine; Bujan, Louis; Marchou, B.; Delobel, Pierre; Gonzalez–Dunia, Daniel; Malnou, Cécile E.; Izopet, Jacques; Martin‐Blondel, Guillaume

doi:10.1016/s1473-3099(16)30336-x

Cited by 152 publications

(145 citation statements)

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“…The persistence of ZIKV in the body for prolonged periods (12) and reports of sexual transmission (10,11) highlight the risks associated with working with infectious virus. The use of VLPs recently emerged as a powerful technology not only to study basic virus biology but also for vaccine and diagnostic assay development (59,60).…”

Section: Discussionmentioning

confidence: 99%

“…In adults, neurological manifestations are characterized by an autoimmune condition with symptoms of neuropathy and paralysis, also known as Guillain-Barré syndrome (8,9). While Aedes species of mosquitos are the most common source of transmission, the virus has also been shown to be transmitted sexually both from women to men and from men to women and is capable of persisting in semen and vaginal secretions for up to 6 months after infection (10)(11)(12).…”

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confidence: 99%

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Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Garg

Sedano

Plata

et al. 2017

J Virol

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Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (CprM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV.IMPORTANCE To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune response. We generated a cell line stably expressing ZIKV prM-E that produces large amounts of VLPs in the supernatant and a ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with a GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP-based vaccines showed significantly better neutralizing antibody responses than those with their DNA counterparts. The RVP-based microneutralization assay worked similarly to the PRNT assay, with a rapid GFP readout in a 96-well format. Our VLP-based platform provides a source for a ZIKV vaccine and diagnosis that can rapidly be adapted to current outbreaks.KEYWORDS C-prM-E, diagnostics, microneutralization, neutralization, PRNT, reporter, reporter virus particles, vaccine, Zika, prM-E S ince the identification of Zika virus (ZIKV) from a rhesus monkey in Uganda in 1947 (1, 2) until 2010, the virus predominantly circulated between Aedes mosquitoes and nonhuman primates. Periodic episodes were inde...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Garg

Sedano

Plata

et al. 2017

J Virol

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“…The characteristics of spermatozoa infection and the time window of risk of sexual transmission are still on debate and the detection of ZIKV on sperm head by immunohistochemistry has been showed [6].…”

Section: Discussionmentioning

confidence: 99%

Persistence of Zika Virus in Gradient Sperm Preparation

Cassuto¹,

Marras²,

Jacomo³

et al. 2017

Andrology

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In April 2016 ZIKA virus RNA was detected during control before performing in vitro fertilization in adult-man semen that contracted the infection in French Guyana and travel back to France. The infection had been detectable in the sperm by qRT-PCR and the virus persists in the semen even after routinely ART sperm migration performed in a bilayer gradient. Zika virus (ZIKV) is an arbovirus transmitted by Aedes aegypti mosquitos. The virus has spread rapidly in the A. aegypti endemic region (South America, Central America, the Caribbean, the Pacific islands, Singapore, and Thailand) but the ability of ZIKV to be transmitted sexually has enhanced the transmission of the disease in non-endemic countries. It has been reported that during pregnancy ZIKV infection can lead to developmental abnormalities (microcephaly, cerebral calcification, fetal loss) and that the virus is also associated with Guillain-Barré syndrome. Guidelines have been drawn up regarding patients who come from countries affected by ZIKV epidemic and who intend to use Assisted Reproductive Technology (ART). The international guidelines impose analysis for ZIKV detection in blood, urine and semen of the patient resident in or travelling back from ZIKV endemic countries in a 6-month-span. These screening analyses must be performed in semen before ART procedures. Keywords: Zika virus; Blood; Semen Case StudyWe report a case of a French man coming to Paris from Guyana, an endemic area, to perform ART for cryptozoospermia diagnostic [1]. The patient described an episode of symptoms compatible with ZIKV which occurred 1 month before his arrival in France: high fever (temperature around 40°C), cephalgia, myalgia and arthralgia.His illness lasted 5 days and he had no symptoms of itchy rash and prostatitis or gross hematospermia. In our laboratory we collected and frozen his semen before the ART attempt [2][3][4][5]. The first standard serologic analysis (HCV, HBV, HIV, TPHA) were negative. But the ZIKV detection was positive by rRT-PCR in both: Total sperm and in the sperm fraction used in ART after bilayer gradient centrifugation. Second tests performed 10 days later detected IgG and IgM in the serum and ZIKV RNA was always present in sperm bilayer gradient preparation. Other control tests have been performed both in ejaculated sperm and in a sperm selected fraction resulting positive. These results have been confirmed by Arbovirus CNR (Marseille). The first negative result appeared on the 112 th day after the onset of symptoms. DiscussionAccording to our knowledge this is the first report in which the ZIKV persists in the fraction. The characteristics of spermatozoa infection and the time window of risk of sexual transmission are still on debate and the detection of ZIKV on sperm head by immunohistochemistry has been showed [6].The viral persistence in semen is one of the key issues and until a solution to this matter can't be found it would be better to follow specific measures of prevention, specifically in the ART procedures. Usually in ART t...

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“…In men, data indicate a high infectious viral load in semen and established sexual transmission from men to women. However, the presence of sperm in the ejaculate indicates a different, probably less radical, pattern of spermatogenic damage in humans compared with mice 8 . Thus, fertility in men could be at risk predominantly owing to transmission of the disease by ZIKV-infected spermatozoa during natural conception or ART, whereas infertility by nonobstructive azoospermia -as seen in mice -could be less of a problem in humans.…”

Section: News and Viewsmentioning

confidence: 93%

A new threat on the horizon — Zika virus and male fertility

Meinhardt

2017

Nat Rev Urol

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Zika virus in semen and spermatozoa

Cited by 152 publications

References 5 publications

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Persistence of Zika Virus in Gradient Sperm Preparation

A new threat on the horizon — Zika virus and male fertility

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