Zika Virus in the Male Reproductive Tract
Abstract
:1. Emergence of Zika Virus
2. Sexual Transmission of ZIKV
3. Persistent Shedding of ZIKV in Semen
4. The MRT and Immune Privilege
5. ZIKV in the Testis and Prostate Gland
6. Mouse Models of ZIKV in the MRT
7. Primate Models of ZIKV Pathogenesis in the MRT
8. Implications for the Development of Therapeutics and Vaccines
9. Concluding Remarks and Future Prospects
- What are the cellular and molecular mechanisms of ZIKV persistence in the MRT?
- What is the origin of ZIKV in semen?
- What is the ZIKV entry receptor in the MRT?
- Which cells in the MRT are primarily infected following ZIKV attachment and entry?
- What are the viral and host characteristics that influence the infectivity and longevity of ZIKV in semen?
Acknowledgments
Conflicts of Interest
Glossary
Arthralgia | Non-inflammatory joint pain. |
Blood-testis-barrier | Physical barrier between blood vessels and the Sertoli cells of the seminiferous tubules in the mammalian testes. |
Conjunctivitis | Inflammation of the outer layer of the eye and inside of the eyelid that causes the eye to turn pink. |
Cryptorchidia | Condition in which one or both of the testes fail to descend from the abdomen into the scrotum. |
Encephalitis | Inflammation of the brain. |
Epididymis | Highly convoluted duct behind the testis, along which sperm passes to the vas deferens. |
Guillain-Barré syndrome (GBS) | Autoimmune disease where antibodies and lymphocytes attack and damage the peripheral nerves causing weakness/paralysis and/or abnormal sensations and pain. |
Hematospermia | Blood in the semen. |
Hypospadias | A congenital condition in males in which the opening of the urethra is on the underside of the penis. |
Ifnar1−/− × Ifngr−/− (AG129) mice | Interferon alpha, beta and gamma receptor deficient mice on a 129 background. |
Ifnar1−/− mice | Interferon alpha and beta receptor deficient mice. |
Immune-privileged site | Sites that are able to tolerate the introduction of antigens without eliciting an inflammatory immune response. Immune-privileged sites include the central nervous system, the brain, the eye, and regions of the male reproductive tract. |
Irf3−/− × Irf7−/− mice | Interferon 3 and 7 double knockout mice. |
Leydig cells | Testosterone-producing cells located in the connective tissue surrounding the seminiferous tubules in the testicle. |
Male accessory glands | In humans, these are the seminal vesicles, prostate gland, and the bulbourethral glands. |
Microcephaly | Medical condition in which the brain does not develop properly resulting in a smaller than normal head. |
Microhematospermia | Hematospermia not evident by macroscopic examinations of the semen, but detected by tests for occult blood. |
Micropenis | An unusually small penis. |
Myalgia | Pain in a muscle or group of muscles. |
Organoids | Three-dimensional cell cultures that incorporate some of the key features of the represented organ. |
Prostatitis | Inflammation of the prostate gland. |
Rag1−/− mice | Recombination activating gene 1 (Rag1) deficient mice. |
Seminal glands | Accessory glands of the MRT, located between the bladder and the rectum that contribute approximately 60–70% of the ejaculate. |
Seminiferous tubules | The site of the germination, maturation, and transportation of the sperm cells within the male testis. |
Sertoli cells | Somatic cells of the testis that are part of a seminiferous tubule and facilitate the nourishment and progression of germ cells to spermatozoa. |
Spermatocytes | Diploid cells formed through the process of spermatogenesis. |
Spermatogenesis | The origin and development of the sperm cells within the male reproductive organs. |
Spermatogonia | Undifferentiated male germ cell, formed in the wall of a seminiferous tubule and giving rise by mitosis to spermatocytes. |
Spermatozoa | The mature motile male sex cell. |
Testicular atrophy | Medical condition in which the testes diminish in size and may be accompanied by loss of function. |
Testicular macrophages | Antigen-presenting cells, the most prevalent cell type in the testicular interstitium. They are in close morphological association and functional interaction with Leydig cells. |
The male reproductive tract (MRT) | The male gonads, associated ducts and glands, and external genitalia that function during procreation. |
Thrombocytopenia | Condition characterized by abnormally low levels of thrombocytes, also known as platelets, in the blood. This causes bleeding into the tissues, bruising, and slow blood clotting after injury. |
Vas deferens | Tiny muscular tube in the MRT that carries sperm from the epididymis to the ejaculatory duct. |
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Mouse Genotype (Background). | ZIKV Genotype (Strain) | Inoculation Route | Testis (Infected Cells) | Epididymis | Seminal Vesicles | Vas Deferens | Prostate | Ref. |
---|---|---|---|---|---|---|---|---|
Wild Type (BALB/c) Dexamethasone Tx | Asian (PRVABC59) | IP | + (ND) | + | ND | ND | + | [88] |
Wild Type (C57BL/6) + | Asian (H/FP/2013) | SC | + (SG, PS, ST, LC) | + | ND | ND | ND | [76] |
anti-IFNαβR mAb | Afr (Dakar 41519) | SC | + (SG, PS, ST, LC) | + | ND | ND | ND | [76] |
Rag1−/− (C57BL/6) + anti-IFNαβR mAb | Asian (Paraiba_01/2015) | IP | + (SG, PS) | ND | ND | ND | ND | [83] |
Ifnar1−/− (C57BL/6) | Asian (ZIKV_SMGC-1) | IP | + (LC, GC, PMC, SG) | + | − | ND | − | [77] |
Asian (Mex2-81) | SC | + (LC) | + | ND | ND | ND | [78] | |
Asian (PRVABC59) | SC | + (ND) | ND | ND | ND | ND | [82] | |
Asian (PRVABC59) | SC | + (ST, MSC) | + | ND | ND | ND | [87] | |
Asian (H/FP/2013) | SC | + (ND) | ND | ND | ND | ND | [85] | |
Asian (PRVABC59) | SC | + (ST) | + | − | ND | + | [89] | |
Asian (Mex2-81) | SC | + (SG) | + | ND | ND | ND | [52] | |
Asian (ZIKVNatal) | SC | +(ND) | ND | ND | ND | ND | [90] | |
(A129) | Asian (PRVABC59) | SC | + (ND) | − | ND | ND | ND | [86] |
Asian (PRVABC59) | IP | + (ND) | ND | ND | ND | ND | [81] | |
African (MP1751) | SC | + (ND) | + | ND | ND | ND | [86] | |
Ifnar1−/− × Ifngr−/− (AG129) | Asian (PRVABC59) | SC | + (LC) | + | + | ND | + | [89] |
Asian (PRVABC59/FSS13025/P6-740) | SC | + (ND) | + | + | ND | ND | [31] | |
Asian (PRVABC59) | IP | + (SG) | + | + | ND | ND | [84] | |
African (Dakar 41524) | SC | + (ND) | + | + | ND | ND | [31] | |
(AG6) | Asian (CAS-ZK01) | SC | + (ST, MC) | ND | ND | ND | ND | [79] |
Irf3−/− × Irf7−/− (C57BL/6) | African (MR766) | SC | + (GC) | + | ND | + | ND | [80] |
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Stassen, L.; Armitage, C.W.; Van der Heide, D.J.; Beagley, K.W.; Frentiu, F.D. Zika Virus in the Male Reproductive Tract. Viruses 2018, 10, 198. https://doi.org/10.3390/v10040198
Stassen L, Armitage CW, Van der Heide DJ, Beagley KW, Frentiu FD. Zika Virus in the Male Reproductive Tract. Viruses. 2018; 10(4):198. https://doi.org/10.3390/v10040198
Chicago/Turabian StyleStassen, Liesel, Charles W. Armitage, David J. Van der Heide, Kenneth W. Beagley, and Francesca D. Frentiu. 2018. "Zika Virus in the Male Reproductive Tract" Viruses 10, no. 4: 198. https://doi.org/10.3390/v10040198