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• W2523646580 abstract "The current Zika virus epidemic is a major challenge for the medical and scientific communities for at least two reasons: the severe clinical situation associated with Zika virus infection (neurological complications and adverse fetal outcomes) and the unexpected sexual viral transmission from men to women.1Petersen LR Jamieson DJ Powers AM Honein MA Zika virus.N Engl J Med. 2016; 374: 1552-1563Crossref PubMed Scopus (875) Google Scholar These recent findings have shifted the paradigm of arbovirus–host interactions, modifying standard epidemiology and clinical patterns. High infectious Zika virus loads have been detected in semen,2Mansuy JM Dutertre M Mengelle C et al.Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen?.Lancet Infect Dis. 2016; 16: 405Summary Full Text Full Text PDF PubMed Scopus (290) Google Scholar but data for viral persistence after symptomatic infections are scarce and even non-existent for asymptomatic ones, with the remaining key issue: how long does semen contain infectious Zika virus? As long as this question is unanswered, the adaptation of preventive measures such as the use of condoms and the abstinence of semen donation will be hampered. Here, we report the longitudinal follow up of Zika virus RNA in the semen of a 32-year-old man returning from French Guyana. At admission, the patient had moderate fever, maculopapular rash, myalgia, and arthralgia and was diagnosed for Zika virus infection upon detection of viral RNA in plasma and urine 2 days after onset of symptoms. The molecular diagnosis for dengue and chikungunya viruses was negative (in-house RT-PCR). The patient was seronegative for HIV, had a normal immunological status, and recovered in few days. Semen (11 samples), blood (ten), and urine (five) were prospectively collected for 141 days after symptom onset. Zika virus RNA was detected on each semen sample and was still positive after 141 days, with viral load decreasing from 8·6 log copies per mL to 3·5 log copies per mL. It was detected until day 37 in both blood (2·5 log copies per mL) and urine (3·7 log copies per mL; figure). Such a prolonged RNA Zika virus excretion is quite different from other flaviviruses, which are rapidly cleared by the immune response and for which the detection of viral nucleic acids is typically limited to a short window after symptom onset. In addition to the present case, we investigated five other symptomatic men for the presence of Zika virus RNA in semen; RNA was still detected 69 days and 115 days after the symptom onset in two patients, but not detected at day 20 in the other three individuals (data not shown). These data suggest that the length of Zika virus excretion varies, probably depending on viral and host characteristics, but long-lasting excretion might be frequent among adults who experienced a symptomatic infection. Such long-lasting excretion of genomic material was recently described in semen from Ebola survivors.3Sow MS Etard JF Baize S et al.New evidence of long-lasting persistence of Ebola virus genetic material in semen of survivors.J Infect Dis. 2016; (published online May 3.)https://doi.org/10.1093/infdis/jiw078Crossref Scopus (62) Google Scholar The viral persistence in semen is of major concern and could be related to a viral tropism for male sexual cells. Accordingly, we report the immunohistochemical detection of Zika virus in the head of spermatozoa obtained from the first patient (figure; appendix). The proportion of infected spermatozoa was estimated at 3·52% (SD 0·71), as assessed by counting Zika-virus-positive spermatozoa on three smears by fluorescence microscopy. The use of both confocal and stimulated emission depletion microscopy (appendix), allowed the unambiguous demonstration that Zika virus antigens are indeed present inside spermatozoa. Additional immunostainings of sperm from a healthy non-infected control donor for Zika virus antigens or with a mouse IgG2a isotype control confirmed the specificity of the staining (data not shown). Spermatozoa do not express the candidate Zika virus entry receptor Axl.4Hamel R Dejarnac O Wichit S et al.Biology of Zika virus infection in human skin cells.J Virol. 2015; 89: 8880-8896Crossref PubMed Scopus (823) Google Scholar Because Sertoli cells highly express Axl and have essential roles in spermatogenesis,5Lu Q Gore M Zhang Q et al.Tyro-3 family receptors are essential regulators of mammalian spermatogenesis.Nature. 1999; 398: 723-728Crossref PubMed Scopus (394) Google Scholar we hypothesise that they might be involved in Zika virus transmission to spermatozoa. Appropriately designed studies are needed to discover the modes of spermatozoa infection and length of risk of sexual transmission. Answers to these questions will allow public health authorities to recommend urgently needed universal safe practices. We declare no competing interests. We thank Sophie Allart (cellular imaging facility of INSERM UMR 1043) and Isabelle Da Silva (Laboratoire de virologie) for instrumental assistance. Download .pdf (.2 MB) Help with pdf files Supplementary appendix" @default.
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• W2523646580 title "Zika virus in semen and spermatozoa" @default.
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