Dataset Information

Maternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive Baboons.

ABSTRACT: Zika virus (ZIKV) infection is now firmly linked to congenital Zika syndrome (CZS), including fetal microcephaly. While Aedes species of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse, and nonhuman primate (NHP) semen. It is critical to establish NHP models of the vertical transfer of ZIKV that recapitulate human pathogenesis. We hypothesized that vaginal deposition of ZIKV-infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Epidemiological studies suggest an increased rate of CZS in the Americas compared to the original link to CZS in French Polynesia; therefore, we also compared the French Polynesian (FP) ZIKV isolate to the Puerto Rican (PR) isolate. Timed-pregnant baboons (n?=?6) were inoculated via vaginal deposition of baboon semen containing 106 focus-forming units (FFU) of ZIKV (n?=?3 for FP isolate H/PF/2013; n?=?3 for PR isolate PRVABC59) at midgestation (86 to 95?days of gestation [dG]; term, 183 dG) on day 0 (all dams) and then at 7-day intervals through 3 weeks. Maternal blood, saliva, and cervicovaginal wash (CVW) samples were obtained. Animals were euthanized at 28 days (n?=?5) or 39 days (n?=?1) after the initial inoculation, and maternal/fetal tissues were collected. Viremia was achieved in 3/3 FP ZIKV-infected dams and 2/3 PR ZIKV-infected dams. ZIKV RNA was detected in CVW samples of 5/6 dams. ZIKV RNA was detected in lymph nodes but not the ovaries, uterus, cervix, or vagina in FP isolate-infected dams. ZIKV RNA was detected in lymph nodes (3/3), uterus (2/3), and vagina (2/3) in PR isolate-infected dams. Placenta, amniotic fluid, and fetal tissues were ZIKV RNA negative in the FP isolate-infected dams, whereas 2/3 PR isolate-infected dam placentas were ZIKV RNA positive. We conclude that ZIKV-infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of widespread dissemination to tissues, including reproductive tissues and placenta, than the FP isolate.IMPORTANCE Zika virus remains a worldwide health threat, with outbreaks still occurring in the Americas. While mosquitos are the primary vector for the spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to an uninfected partner. While sexual transmission has been documented in humans, and male-to-female transmission has been reported in mice, ours is the first study in nonhuman primates to demonstrate infection via vaginal deposition of Zika virus-infected semen. The latter is important since a recent publication indicated that human semen inhibited, in a laboratory setting, Zika virus infection of reproductive tissues. We also found that compared to the French Polynesian isolate, the Puerto Rican Zika virus isolate led to greater spread throughout the body, particularly in reproductive tissues. The American isolates of Zika virus appear to have acquired mutations that increase their efficacy.

SUBMITTER: Gurung S

PROVIDER: S-EPMC7269433 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Maternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive Baboons.

Gurung Sunam S Nadeau Hugh H Maxted Marta M Peregrine Jamie J Reuter Darlene D Norris Abby A Edwards Rodney R Hyatt Kimberly K Singleton Krista K Papin James F JF Myers Dean A DA

Journal of virology 20200518 11

Zika virus (ZIKV) infection is now firmly linked to congenital Zika syndrome (CZS), including fetal microcephaly. While <i>Aedes</i> species of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse, and nonhuman primate (NHP) semen. It is critical to establish NHP models of the vertical transfer of ZIKV that recapitulate human pathogenesis. We hypothesized that vaginal deposition of ZIKV-infected baboon ...[more]

PMID: 32188737

Similar Datasets

Project description:Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM) by vaginal inoculation with 104-106 plaque-forming units (PFU). However, there was variability in susceptibility between the individual RM with 1->8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ) virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT) secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and pathology after vaginal ZIKV transmission compared to a mosquito transmitted ZIKV.

Project description:Pathogens exert a profound and pervasive cost on various aspects of primate sociality and reproduction. In olive baboons (Papio anubis) at Lake Manyara National Park, Tanzania, genital skin ulcers, caused by the bacterium Treponema pallidum subsp. pertenue, are associated with increased female mating avoidance and altered male mating patterns at a pre-copulatory and copulatory level. Beyond this, mating is also comprised of post-copulatory interactions among sexual partners (i.e., copulation calls, darting [post-copulatory sprint away from the male], and post-copulatory grooming). In baboons, female post-copulatory behavior is hypothesized to incite male-male competition, promote subsequent copulations, and/or strengthen the bonds between the mating pairs. Due to a higher reproductive burden (i.e. pregnancy, lactation, infant rearing), females should avoid proceptive behavior after mating to decrease further exposure to potential pathogens. To investigate whether the presence of genital skin ulcers has an impact at the post-copulatory level, we analyzed 517 copulation events of 33 cycling females and 29 males with and without genital skin ulcers. The occurrence of female post-copulatory behaviors was not altered by genital skin ulcerations in males. Similar to other baboon populations, females in our study group were more likely to utter copulation calls after an ejaculatory copulation. The likelihood of darting was higher after ejaculatory copulations and with the presence of copulation calls. Post-copulatory grooming (i.e., occurring within 15 seconds after a copulation) was not frequently observed. Our results indicate that despite the presence of conspicuous signs of disease, female post-copulatory behavior was not affected by the genital health status of the males. This indicates that in our study group, infection cues caused by T. pallidum subsp. pertenue play a major role before and during mating, but not after mating. The post-copulatory behavior of females is most likely affected by physiological or evolutionary constraints other than sexually transmitted infections.

Dataset Information

Maternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive Baboons.

Publications

Maternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive Baboons.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets