Cellular Targets and Receptor of Sexual Transmission of Zika Virus
| Autor: | Gregory R. Goodwin, Brandon W. Hughes, Pratima Pandey, Omar Bagasra, Krishna C. Addanki, Ewen McLean |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Permissiveness Male Histology Sexual transmission Semen Viremia Biology Real-Time Polymerase Chain Reaction Virus Pathology and Forensic Medicine Zika virus 03 medical and health sciences 0302 clinical medicine medicine Humans 030212 general & internal medicine urogenital system Zika Virus Infection Receptor Protein-Tyrosine Kinases Zika Virus Sperm bank biology.organism_classification medicine.disease Sperm Virology Spermatozoa Medical Laboratory Technology 030104 developmental biology Immunology |
| Zdroj: | Applied immunohistochemistrymolecular morphology : AIMM. 25(10) |
| ISSN: | 1533-4058 |
| Popis: | Study question What is the mechanism of sexual transmission of Zika virus (ZIKV)? Summary answer By utilizing exquisite reverse transcriptase-initiated in situ polymerase chain reaction (RT-in situ PCR), which enables an improved visualization of spermatozoa's subcellular compartment, we precisely localized the mid-piece of sperm that carry receptors for ZIKV. What is already known ZIKV is transmitted sexually and recent studies have verified ZIKV presence in semen of previously Zika-infected patients for >6-month postinfection when ZIKV had disappeared from blood, saliva, and urine. Strong serial analyses of various body fluids suggest that ZIKV can be transmitted between sexual partners. Currently, there is limited information on the association of the virus with human semen cell types that may carry the virus. Study design, size, duration Analyses were carried out to localize ZIKV for subcellular localization of ZIKV on cell types. The Tyro3 receptor for ZIKV was colocalized by dual immunocytochemistry with specific monoclonal antibodies. Participants/materials, setting, methods Three semen specimens were purchased from a commercial sperm bank. Motile sperm was separated from nonmotile cells by the "swim-up" technique. Each of the semen fractions was infected with ZIKV at the multiplicity of infection of 0.1.0 and 1.0 and evaluated for the primary targets of ZIKV in the semen cells by RT-in situ PCR and confirmed by real-time RT-PCR. Main results and the role of chance ZIKV was present primarily at the mid-piece of mature spermatozoa in about 30% of the sperm. In addition, we determined that Tyro3 receptors, primarily expressed on mid-piece of human spermatozoa, play a role in ZIKV-binding and entry into spermatozoa. Our data strongly suggest a potential sexual/horizontal route of transmission for ZIKV primarily via infected sperms; most likely ZIKV enters the sperm via the Tyro3 receptor found at the mid-piece of the mature spermatozoa. Limitations, reasons for caution We are uncertain as to what phase of spermatogenesis, that in human takes about 120 days, sperms are permissive to ZIKV. If permissiveness was very early during spermatogenesis males could be infectious for ∼120 days after the disappearance of viremia in an infected man. Wider implications of the findings Our findings bring a new focus on the current affords to develop ZIKV vaccine. Why in the presence of anti-ZIKV antibodies infected men are still able to transmit the virus sexually? We suggest that only certain subclass of immunoglobulin (Ig)G (ie, IgG4) can cross the blood-Sertoli barrier therefore, a successful vaccine must provoke a subclass of IgG can quell ZIKV inside the seminiferous tubules. |
| Databáze: | OpenAIRE |
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