scholarly journals Zika Virus Trafficking and Interactions in the Human Male Reproductive Tract

Pathogens ◽  
2018 ◽  
Vol 7 (2) ◽  
pp. 51 ◽  
Author(s):  
Lucia Da Silva
Keyword(s):  
Zika Virus ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Host Cells ◽  
Future Research ◽  
Mosquito Vector ◽  
Male Reproductive Tract ◽  
Unprotected Sexual Intercourse ◽  
Human Male ◽  
Viral Interactions

Sexual transmission of Zika virus (ZIKV) is a matter of great concern. Infectious viral particles can be shed in semen for as long as six months after infection and can be transferred to male and female sexual partners during unprotected sexual intercourse. The virus can be found inside spermatozoa and could be directly transferred to the oocyte during fertilization. Sexual transmission of ZIKV can contribute to the rise in number of infected individuals in endemic areas as well as in countries where the mosquito vector does not thrive. There is also the possibility, as has been demonstrated in mouse models, that the vaginal deposition of ZIKV particles present in semen could lead to congenital syndrome. In this paper, we review the current literature to understand ZIKV trafficking from the bloodstream to the human male reproductive tract and viral interactions with host cells in interstitial spaces, tubule walls, annexed glands and semen. We hope to highlight gaps to be filled by future research and potential routes for vaccine and antiviral development.

scholarly journals Animal Models of Zika Virus Infection, Pathogenesis, and Immunity

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Thomas E. Morrison ◽  
Michael S. Diamond
Keyword(s):  
Animal Models ◽  
Virus Infection ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Scientific Community ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Rapid Testing ◽  
Zikv Infection ◽  
Male Reproductive Tract

ABSTRACT Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis.

scholarly journals Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 291
Author(s):  
Erika R. Schwarz ◽  
Lilian J. Oliveira ◽  
Francesco Bonfante ◽  
Ruiyu Pu ◽  
Malgorzata A. Pozor ◽  
...  
Keyword(s):  
Zika Virus ◽  
Post Infection ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Infection Model ◽  
Intact Male ◽  
Zikv Infection ◽  
Male Reproductive Tract ◽  
Pregnant Sheep ◽  
Male Sheep

Zika virus (ZIKV) is an arbovirus that causes birth defects, persistent male infection, and sexual transmission in humans. The purpose of this study was to continue the development of an ovine ZIKV infection model; thus, two experiments were undertaken. In the first experiment, we built on previous pregnant sheep experiments by developing a mid-gestation model of ZIKV infection. Four pregnant sheep were challenged with ZIKV at 57–64 days gestation; two animals served as controls. After 13–15 days (corresponding with 70–79 days of gestation), one control and two infected animals were euthanized; the remaining animals were euthanized at 20–22 days post-infection (corresponding with 77–86 days of gestation). In the second experiment, six sexually mature, intact, male sheep were challenged with ZIKV and two animals served as controls. Infected animals were serially euthanized on days 2–6 and day 9 post-infection with the goal of isolating ZIKV from the male reproductive tract. In the mid-gestation study, virus was detected in maternal placenta and spleen, and in fetal organs, including the brains, spleens/liver, and umbilicus of infected fetuses. Fetuses from infected animals had visibly misshapen heads and morphometrics revealed significantly smaller head sizes in infected fetuses when compared to controls. Placental pathology was evident in infected dams. In the male experiment, ZIKV was detected in the spleen, liver, testes/epididymides, and accessory sex glands of infected animals. Results from both experiments indicate that mid-gestation ewes can be infected with ZIKV with subsequent disruption of fetal development and that intact male sheep are susceptible to ZIKV infection and viral dissemination and replication occurs in highly vascular tissues (including those of the male reproductive tract).

scholarly journals Zika Virus Causes Acute and Chronic Prostatitis in Mice and Macaques

2019 ◽  
Vol 221 (9) ◽  
pp. 1506-1517 ◽  
Author(s):  
Jacques Halabi ◽  
Brett W Jagger ◽  
Vanessa Salazar ◽  
Emma S Winkler ◽  
James P White ◽  
...  
Keyword(s):  
Zika Virus ◽  
Chronic Prostatitis ◽  
Animal Studies ◽  
Reproductive Tract ◽  
Rhesus Macaques ◽  
Sexual Transmission ◽  
Vital Role ◽  
Male Reproductive Tract ◽  
Virus Clearance ◽  
Sperm Counts

Abstract Background Sexual transmission and persistence of Zika virus (ZIKV) in the male reproductive tract has raised concerned for potential damaging effects on function. Animal studies have demonstrated that ZIKV virus can infect and damage the testis and epididymis, and these results has been correlated to lower sperm counts in ZIKV-infected humans. The prostate plays a vital role in the male reproductive tract, with acute and chronic prostatitis linked to male infertility. Methods In this study, we evaluated the effects of ZIKV virus on the prostate in mice and nonhuman primates. Results In mice, ZIKV infected the prostate and triggered inflammation that persisted even after virus clearance. Evidence of chronic prostatitis associated with ZIKV infection remained for several months. Similar histological findings were observed in the prostate of ZIKV-infected rhesus macaques. Conclusions These studies establish that ZIKV replicates in the prostate and can cause acute and chronic inflammatory and proliferative changes in mouse and nonhuman primate models.

scholarly journals Persistence of Zika virus RNA in the epididymis of the male reproductive tract

2020 ◽  
Author(s):  
Megan B. Vogt ◽  
Francesca Frere ◽  
Seth A. Hawks ◽  
Claudia E. Perez ◽  
Sheryl Coutermarsh-Ott ◽  
...  
Keyword(s):  
Birth Defects ◽  
Persistent Infection ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Infectious Virus ◽  
Sexual Transmission ◽  
In Utero ◽  
Zikv Infection ◽  
Male Reproductive Tract ◽  
Health Decisions

ABSTRACTZika virus (ZIKV) can infect developing fetuses in utero and cause severe congenital defects. This in utero transmission can occurs following ZIKV infection during pregnancy via sexual transmission or mosquito bite. Infected men may shed ZIKV RNA in semen for over six months post symptom onset, indicating that ZIKV may persistently infect the male reproductive tract (MRT). However, the site of persistent infection in the MRT and whether ZIKV can recrudesce in the MRT is unknown. We hypothesized that if ZIKV establishes a persistent infection in the MRT, then immunosuppressant treatment should stimulate ZIKV replication. We tested this hypothesis in a wild-type mouse model of ZIKV sexual transmission. Male mice were infected with ZIKV and immunosuppressed when they no longer shed infectious virus in their ejaculates. After immunosuppression, ejaculates and MRT tissues were monitored for infectious virus and ZIKV RNA. Our results show that ZIKV recrudescence did not occur following immunosuppression, as we did not detect significant levels of infectious virus in ejaculates or MRT tissues following immunosuppression. We did detect ZIKV RNA in the epididymides of mice treated with the immunosuppressant cyclophosphamide. Further analysis revealed that this ZIKV RNA was contained within the lumen of the epididymis. Our findings suggest that ZIKV persistently infects the epididymis within the male reproductive tract. This study provides insight into the mechanisms behind ZIKV sexual transmission, which may inform public health decisions regarding ZIKV risks.ImportanceZika virus (ZIKV) is an emerging mosquito-transmitted virus that typically causes mild and self-limiting febrile illness in humans; however, during the recent epidemic of ZIKV in the Americas, severe birth defects, such as microcephaly and club foot, were reported in infants born to ZIKV infected mothers. Additionally, sexual transmission has been identified as a secondary method of ZIKV transmission. Since ZIKV can be isolated from semen of infected men long after initial infection, it is imperative to understand the mechanism(s) of ZIKV infection of the male reproductive tract to prevent sexual transmission and ZIKV-associated birth defects. The significance of our research is in identifying a site of persistent ZIKV infection in the male reproductive tract and in assessing the likelihood that a persistently infected individual will begin shedding infectious virus in semen again. This information will enhance our understanding of ZIKV sexual transmission and inform health decisions regarding ZIKV risks.

scholarly journals Cellular and Humoral Immunity Protect against Vaginal Zika Virus Infection in Mice

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Jason M. Scott ◽  
Tania J. Lebratti ◽  
Justin M. Richner ◽  
Xiaoping Jiang ◽  
Estefania Fernandez ◽  
...  
Keyword(s):  
T Cells ◽  
Pregnant Women ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Female Reproductive Tract ◽  
Mosquito Vector ◽  
Zikv Infection ◽  
Correlates Of Protection ◽  
Immune Correlates

ABSTRACTZika virus (ZIKV), which can cause devastating disease in fetuses of infected pregnant women, can be transmitted by mosquito inoculation and sexual routes. Little is known about immune protection against sexually transmitted ZIKV. In this study, we show that previous infection through intravaginal or subcutaneous routes with a contemporary Brazilian strain of ZIKV can protect against subsequent intravaginal challenge with a homologous strain. Both routes of inoculation induced high titers of ZIKV-specific and neutralizing antibody in serum and the vaginal lumen. Virus-specific T cells were recruited to and retained in the female reproductive tract after intravaginal and subcutaneous ZIKV infection. Studies in mice with genetic or acquired deficiencies in B and/or T cells demonstrated that both lymphocyte populations redundantly protect against intravaginal challenge in ZIKV-immune animals. Passive transfer of ZIKV-immune IgG or T cells significantly limited intravaginal infection of naive mice, although antibody more effectively prevented dissemination throughout the reproductive tract. Collectively, our experiments begin to establish the immune correlates of protection against intravaginal ZIKV infection, which should inform vaccination strategies in nonpregnant and pregnant women.IMPORTANCEThe recent ZIKV epidemic resulted in devastating outcomes in fetuses and may affect reproductive health. Unlike other flaviviruses, ZIKV can be spread by sexual contact as well as a mosquito vector. While previous studies have identified correlates of protection for mosquito-mediated infection, few have focused on immunity against sexual transmission. As exposure to ZIKV via mosquito bite has likely occurred to many living in areas where ZIKV is endemic, our study addresses whether this route of infection can protect against subsequent sexual exposure. We demonstrate that subcutaneous ZIKV infection can protect against subsequent vaginal infection by generating both local antiviral T cell and antibody responses. Our research begins to define the immune correlates of protection for ZIKV infection in the vagina and provides a foundation for testing ZIKV vaccines against sexual transmission.

scholarly journals From Mosquito Bites to Sexual Transmission: Evaluating Mouse Models of Zika Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2244
Author(s):  
Elizabeth Balint ◽  
Amelia Montemarano ◽  
Emily Feng ◽  
Ali A. Ashkar
Keyword(s):  
Mouse Models ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Zikv Infection ◽  
Sexually Transmitted ◽  
Advantages And Disadvantages ◽  
Effective Use ◽  
The Impact ◽  
Male To Female

Following the recent outbreak of Zika virus (ZIKV) infections in Latin America, ZIKV has emerged as a global health threat due to its ability to induce neurological disease in both adults and the developing fetus. ZIKV is largely mosquito-borne and is now endemic in many parts of Africa, Asia, and South America. However, several reports have demonstrated persistent ZIKV infection of the male reproductive tract and evidence of male-to-female sexual transmission of ZIKV. Sexual transmission may broaden the reach of ZIKV infections beyond its current geographical limits, presenting a significant threat worldwide. Several mouse models of ZIKV infection have been developed to investigate ZIKV pathogenesis and develop effective vaccines and therapeutics. However, the majority of these models focus on mosquito-borne infection, while few have considered the impact of sexual transmission on immunity and pathogenesis. This review will examine the advantages and disadvantages of current models of mosquito-borne and sexually transmitted ZIKV and provide recommendations for the effective use of ZIKV mouse models.

scholarly journals Zika virus in rhesus macaque semen and reproductive tract tissues: a pilot study of acute infection†

2020 ◽  
Vol 103 (5) ◽  
pp. 1030-1042 ◽  
Author(s):  
Jenna K Schmidt ◽  
Katherine D Mean ◽  
Riley C Puntney ◽  
Eric S Alexander ◽  
Ruth Sullivan ◽  
...  
Keyword(s):  
Pilot Study ◽  
Rhesus Macaque ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Acute Infection ◽  
Viral Rna ◽  
Viral Reservoir ◽  
Computer Assisted ◽  
Male Reproductive Tract ◽  
The Impact

Abstract Although sexual transmission of Zika virus (ZIKV) is well-documented, the viral reservoir(s) in the male reproductive tract remains uncertain in humans and immune-intact animal models. We evaluated the presence of ZIKV in a rhesus macaque pilot study to determine persistence in semen, assess the impact of infection on sperm functional characteristics, and define the viral reservoir in the male reproductive tract. Five adult male rhesus monkeys were inoculated with 105 PFU of Asian-lineage ZIKV isolate PRVABC59, and two males were inoculated with the same dose of African-lineage ZIKV DAKAR41524. Viremia and viral RNA (vRNA) shedding in semen were monitored, and a cohort of animals were necropsied for tissue collection to assess tissue vRNA burden and histopathology. All animals exhibited viremia for limited periods (1–11 days); duration of shedding did not differ significantly between viral isolates. There were sporadic low levels of vRNA in the semen from some, but not all animals. Viral RNA levels in reproductive tract tissues were also modest and present in the epididymis in three of five cases, one case in the vas deferens, but not detected in testis, seminal vesicles or prostate. ZIKV infection did not impact semen motility parameters as assessed by computer-assisted sperm analysis. Despite some evidence of prolonged ZIKV RNA shedding in human semen and high tropism of ZIKV for male reproductive tract tissues in mice deficient in Type 1 interferon signaling, in the rhesus macaques assessed in this pilot study, we did not consistently find ZIKV RNA in the male reproductive tract.

scholarly journals Location of a membrane-bound carbonic anhydrase isoenzyme (CA IV) in the human male reproductive tract.

1993 ◽  
Vol 41 (5) ◽  
pp. 751-757 ◽  
Author(s):  
S Parkkila ◽  
A K Parkkila ◽  
K Kaunisto ◽  
A Waheed ◽  
W S Sly ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Carbonic Anhydrase ◽  
Reproductive Tract ◽  
Muscle Layer ◽  
Apical Plasma Membrane ◽  
Specific Staining ◽  
Ductus Deferens ◽  
Male Reproductive Tract ◽  
Human Male ◽  
Membrane Bound

We studied the location of a membrane-bound carbonic anhydrase (CA IV) in the human male reproductive tract using a specific antiserum to human CA IV in conjunction with immunoblotting, immunoperoxidase, and immunofluorescence techniques. The microvilli and apical plasma membrane of the epithelial cells and the subepithelial smooth muscle layer of the epididymis, ductus deferens, and ampulla of the ductus deferens showed specific staining for CA IV. The epithelial cells of the prostate and seminal vesicle failed to stain for CA IV, however, whereas the subepithelial smooth muscle layer showed positive staining. No specific staining for CA II was seen in the epithelium of the epididymal duct or the proximal ductus deferens. The presence of CA IV in the epididymis was confirmed by immunoblotting, which revealed 35 KD and 33 KD polypeptides. The results show that the microvilli and the apical plasma membrane of the lining epithelium of the epididymal duct, ductus deferens, and ampulla of the ductus deferens contain the membrane-bound carbonic anhydrase isoenzyme IV. The presence of the enzyme in the epithelium of the epididymis and ductus deferens is probably linked to the acidification of the epididymal fluid that prevents premature sperm activation. Its physiological role in the smooth muscle cells remains to be elucidated.

scholarly journals Sulfated Glycans and Related Digestive Enzymes in the Zika Virus Infectivity: Potential Mechanisms of Virus-Host Interaction and Perspectives in Drug Discovery

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Vitor H. Pomin
Keyword(s):  
Neural Development ◽  
Zika Virus ◽  
Molecular Mechanisms ◽  
Surface Proteins ◽  
Host Cells ◽  
Future Research ◽  
Virus Infectivity ◽  
Virus Attachment ◽  
Chemical Structures ◽  
Host Interaction

As broadly reported, there is an ongoing Zika virus (ZIKV) outbreak in countries of Latin America. Recent findings have demonstrated that ZIKV causes severe defects on the neural development in fetuses in utero and newborns. Very little is known about the molecular mechanisms involved in the ZIKV infectivity. Potential therapeutic agents are also under investigation. In this report, the possible mechanisms of action played by glycosaminoglycans (GAGs) displayed at the surface proteoglycans of host cells, and likely in charge of interactions with surface proteins of the ZIKV, are highlighted. As is common for the most viruses, these sulfated glycans serve as receptors for virus attachment onto the host cells and consequential entry during infection. The applications of (1) exogenous sulfated glycans of different origins and chemical structures capable of competing with the virus attachment receptors (supposedly GAGs) and (2) GAG-degrading enzymes able to digest the virus attachment receptors on the cells may be therapeutically beneficial as anti-ZIKV. This communication attempts, therefore, to offer some guidance for the future research programs aimed to unveil the molecular mechanisms underlying the ZIKV infectivity and to develop therapeutics capable of decreasing the devastating consequences caused by ZIKV outbreak in the Americas.

scholarly journals STUDY OF CREATINE KINASE-BB IN THE HUMAN MALE REPRODUCTIVE TRACT

1987 ◽  
Vol 78 (12) ◽  
pp. 2071-2078
Author(s):  
Toshio Yoshida
Keyword(s):  
Creatine Kinase ◽  
Reproductive Tract ◽  
Male Reproductive Tract ◽  
Creatine Kinase Bb ◽  
Human Male
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