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 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 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 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 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 1874. Comparison of the Risk of Birth Defects in Live Births From Pregnant Women Infected and Not Infected by Zika Virus in Guadeloupe, 2016–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S47-S47
Author(s):  
Anna Louise Funk ◽  
Bruno Hoen ◽  
Benoit Tressières ◽  
Ingrid Vingadassalom ◽  
Eustase Janky ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pregnant Women ◽  
Birth Defects ◽  
Zika Virus ◽  
Growth Curves ◽  
Neurological Complications ◽  
In Utero ◽  
Control Group ◽  
Zikv Infection ◽  
Neurological Abnormalities

Abstract Background In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was estimated at 7% among fetuses/infants in a cohort of 546 women who developed a symptomatic RT-PCR confirmed ZIKV infection during pregnancy (NEJM 2018;378:985–94). There was no concomitant prospective cohort of pregnant women without ZIKV infection to use as a control group. Methods In Guadeloupe, one of the 3 FTAs that participated in the FTA cohort study, pregnant women were recruited at the time of delivery and tested for ZIKV infection. Women who had a confirmed negative IgG serology test for ZIKV at delivery and no other positive ZIKV test during pregnancy were considered to be ZIKV noninfected. Information on the course of the pregnancy was collected retrospectively and outcomes of live born infants of ZIKV noninfected women were analyzed, using the same definition criteria as those used for the FTA cohort study. Pregnancy outcomes were compared with those of the 241 ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA cohort. Results Of the 490 live born infants without in-utero exposure to ZIKV, 42 infants (8.6%) had neurological abnormalities that were described as “potentially linked to ZIKV infection”; all but one of these were microcephaly without any other brain or clinical abnormalities. The proportion of such abnormalities was not statistically different from that observed in the 241 live born infants with ZIKV exposure (6.6%, P = 0.36). When re-considering the combined 8 fetuses and 241 infants of women with confirmed ZIKV infection in Guadeloupe from the FTA cohort, only two (0.8%) live born infants and three (1.2%) medically aborted fetuses had birth defects that could still be linked to ZIKV infection. Conclusion Isolated anthropometric and other mild neurological abnormalities had the same prevalence among live born infants with and without in utero ZIKV exposure. The high prevalence of isolated microcephaly among ZIKV noninfected women in our study population suggests that the sensitive definition for microcephaly, using a −2 SD cut-off with international growth curves, may lead to an overestimate of the rate of neurological complications of ZIKV infection during pregnancy. Disclosures All Authors: No reported Disclosures.

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 Zika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.

2021 ◽  
Author(s):  
Raissa Rilo Christoff ◽  
Jefferson H. Quintanilha ◽  
Raiane O Ferreira ◽  
Jessica C. C. G. Ferreira ◽  
Daniel Menezes Guimaraes ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Axon Guidance ◽  
Birth Defects ◽  
Zika Virus ◽  
In Utero ◽  
Mouse Embryos ◽  
Rna Seq ◽  
Zikv Infection ◽  
Density Reduction ◽  
Congenital Zika Syndrome

Congenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with Brazilian ZIKV and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed that in utero infection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline.

scholarly journals The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1006 ◽  
Author(s):  
Raquel das Neves Almeida ◽  
Heloisa Antoniella Braz-de-Melo ◽  
Igor de Oliveira Santos ◽  
Rafael Corrêa ◽  
Gary P. Kobinger ◽  
...  
Keyword(s):  
Germ Cells ◽  
Zika Virus ◽  
Male Fertility ◽  
Cellular Response ◽  
Reproductive Tract ◽  
Human Reproduction ◽  
Testicular Atrophy ◽  
Zikv Infection ◽  
Male Reproductive Tract ◽  
Current Vaccine

Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.

scholarly journals Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Julia A. Gomes ◽  
Eduarda Sgarioni ◽  
Juliano A. Boquett ◽  
Ana Cláudia P. Terças-Trettel ◽  
Juliana H. da Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Genetic Variants ◽  
Educational Level ◽  
Congenital Anomalies ◽  
Family Income ◽  
First Trimester ◽  
In Utero ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

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