Male germ cells support long-term propagation of Zika virus

Robinson, Christopher L.; Chong, Angie Chi Nok; Ashbrook, Alison W.; Jeng, Ginnie; Jin, Julia; Chen, Haiqi; Tang, Elizabeth I.; Martin, L. A.; Kim, Rosa S.; Kenyon, Reyn; Do, Eileen; Luna, Joseph M.; Saeed, Mohsan; Zeltser, Lori M.; Ralph, Harold; Dudley, Vanessa; Goldstein, Marc; Rice, Charles M.; Cheng, C. Yan; Seandel, Marco; Chen, Shuibing

doi:10.1038/s41467-018-04444-w

Cited by 76 publications

(74 citation statements)

References 48 publications

(40 reference statements)

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“…This cellular physiology and ZIKV modulation can develop an important factor that may lead to the establishment of viruses in this organ. Other cell types in the testicle can support the ZIKV infection, such as testicular fibroblast, germ cells, and spermatocyte [43,83]. The TAM receptor, AXL, promotes the ZIKV entrance in SCs and contributes negatively to the antiviral states of SCs [82].…”

Section: Zikv On Male Reproductive Tractmentioning

confidence: 99%

“…Microorganisms coming from blood or urogenital infections enter into a testicular environment and disrupt tissue homeostasis, leading to activation of local immune system [3]. This process triggers testicular inflammation and may alter tissue metabolism, signalization, cellular function, and leading to impaired spermatogenesis and spermiogenesis [42,43]. Many pathogens have been shown to cause male infertility by many mechanisms, induced inflammation being the key for most of them.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Almeida

Braz-de-Melo

Santos

et al. 2020

Cells

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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.

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Section: Zikv On Male Reproductive Tractmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Almeida

Braz-de-Melo

Santos

et al. 2020

Cells

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“…Intracellular viral persistence is likely an important component for long-term sexual transmission. Although the cells that act as reservoirs of ZIKV in testes and the reproductive tract are unknown, possible reservoirs in the host are SC [67,68] germ cells [69], Leydig cells [70] and epididymal epithelial cells [59,62] which have been shown to support persistent infections of ZIKV (Figure 1). When primary SCs persistently infected with two strains of ZIKV (PRVABC59 or MR766) were monitored for a period of 6 weeks, it was found that 15% of the cells were still positive for both strains of ZIKV [67].…”

Section: Persistence and Tropism Of Zikv On The Male Reproductive Tractmentioning

confidence: 99%

Animal Models of Zika Virus Sexual Transmission

Campos¹,

McDonald²,

Brault³

et al. 2021

Current Concepts in Zika Research

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ZIKV was first identified in the 1940s as a mosquito-borne virus; however, sexual transmission, which is uncommon for arboviruses, was demonstrated more than 60 years later. Tissue culture and animal models have allowed scientists to study how this transmission is possible. Immunocompromised mice infected with ZIKV had high viral loads in their testes, and infection of immunocompetent female mice was achieved following intravaginal inoculation or inoculation via mating with an infected male. These mouse studies lead researchers to investigate the individual components of the male reproductive system. In cell culture and mouse models, ZIKV can persist in Sertoli and germ cells of the testes and epithelial cells in the epididymis, which may lead to sexual transmission even after ZIKV has been cleared from other tissues. ZIKV has also been studied in nonhuman primates (NHPs), which appears to mimic the limited human epidemiological data, with low rates of symptomatic individuals and similar clinical signs. Although refinement is needed, these animal models have proven to be key in ZIKV research and continue to help uncovering the mechanisms of sexual transmission. This review will focus on the animal models used to elucidate the mechanisms of sexual transmission and persistence of flaviviruses.

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“…LSM14A, a host restriction factor required for viral sensing and interferon induction was the most downregulated transcript in the ZIKV infected cells . Immune‐staining studies on human testicular tissue biopsy samples exposed to ZIKV indicated that human germ cells supported viral replication . ZIKV infection of cells of testis can affect the architecture of the organ.…”

Section: Pathophysiologymentioning

confidence: 99%

Zika virus: Molecular responses and tissue tropism in the mammalian host

Shaily

Upadhya

2019

Reviews in Medical Virology

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Zika virus (ZIKV) outbreaks have raised alarm because of reports of congenital Zika virus syndrome in infants. The virus is also known to cause the debilitating Guillain-Barré syndrome in adults. As a result, extensive research has been carried out on the virus over the past few years. To study the molecular responses of viral infectivity in mammals, in vitro two-dimensional and three-dimensional cellular models have been employed. The in vivo models of mouse, pig, chicken, and nonhuman primates are primarily used to investigate the teratogenicity of the virus, to study effects of the virus on specific tissues, and to study the systemic effects of a proposed antiviral agent. The virus exhibits wide tissue tropism in the mammalian host.

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Male germ cells support long-term propagation of Zika virus

Cited by 76 publications

References 48 publications

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

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

Animal Models of Zika Virus Sexual Transmission

Zika virus: Molecular responses and tissue tropism in the mammalian host

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