Human Testicular Germ Cells, a Reservoir for Zika Virus, Lack Antiviral Response Upon Zika or Poly(I:C) Exposure

Kuassivi, Ohiniba Nadège; Abiven, Hervé; Satie, Anne‐Pascale; Cartron, Matéo; Mahé, Dominique; Aubry, Fabien; Mathiéu, Romain; Rebours, Valérie; Tortorec, Anna Le; Dejucq-Rainsford, Nathalie

doi:10.3389/fimmu.2022.909341

Cited by 9 publications

(8 citation statements)

References 44 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Instead, oocytes show an efficient RNA interference (RNAi) response, an antiviral system classically attributed to non-vertebrate organisms, which will be described in more detail in the next section [ 18 , 19 ]. Similar observations have been made in rat spermatogonia and human testis explants, which both fail to induce an IFN response upon viral infection or dsRNA (poly I:C) treatment [ 20 , 21 , 22 ]. These results suggest that the absence of a functional IFN response is characteristic of pluripotent cells, as well as gametes.…”

Section: The Type-i Ifn Response and Early Developmentsupporting

confidence: 70%

Antiviral Defence Mechanisms during Early Mammalian Development

Mueller,

Witteveldt,

Macias

2024

Viruses

View full text Add to dashboard Cite

The type-I interferon (IFN) response constitutes the major innate immune pathway against viruses in mammals. Despite its critical importance for antiviral defence, this pathway is inactive during early embryonic development. There seems to be an incompatibility between the IFN response and pluripotency, the ability of embryonic cells to develop into any cell type of an adult organism. Instead, pluripotent cells employ alternative ways to defend against viruses that are typically associated with safeguard mechanisms against transposable elements. The absence of an inducible IFN response in pluripotent cells and the constitutive activation of the alternative antiviral pathways have led to the hypothesis that embryonic cells are highly resistant to viruses. However, some findings challenge this interpretation. We have performed a meta-analysis that suggests that the susceptibility of pluripotent cells to viruses is directly correlated with the presence of receptors or co-receptors for viral adhesion and entry. These results challenge the current view of pluripotent cells as intrinsically resistant to infections and raise the fundamental question of why these cells have sacrificed the major antiviral defence pathway if this renders them susceptible to viruses.

show abstract

Section: The Type-i Ifn Response and Early Developmentsupporting

confidence: 70%

Antiviral Defence Mechanisms during Early Mammalian Development

Mueller,

Witteveldt,

Macias

2024

Viruses

View full text Add to dashboard Cite

show abstract

“…ZIKV infection is widely recognized as significantly reducing spermatogenesis after producing major physiological, immunological, and endocrine damage in the testes, most likely owing to YBX2 subtraction dysregulation. Male sensitivity to flavivirus infection may be due to YBX2 expression in testicular germ cells, as evidenced by the greater incidence of antibodies in males (32.3%) compared to females [ 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

The Continuous Adaptive Challenge Played by Arboviruses: An In Silico Approach to Identify a Possible Interplay between Conserved Viral RNA Sequences and Host RNA Binding Proteins (RBPs)

Chetta¹,

Cammarota

Marco

et al. 2023

IJMS

View full text Add to dashboard Cite

Climate change and globalization have raised the risk of vector-borne disease (VBD) introduction and spread in various European nations in recent years. In Italy, viruses carried by tropical vectors have been shown to cause viral encephalitis, one of the symptoms of arboviruses, a spectrum of viral disorders spread by arthropods such as mosquitoes and ticks. Arboviruses are currently causing alarm and attention, and the World Health Organization (WHO) has released recommendations to adopt essential measures, particularly during the hot season, to restrict the spreading of the infectious agents among breeding stocks. In this scenario, rapid analysis systems are required, because they can quickly provide information on potential virus–host interactions, the evolution of the infection, and the onset of disabling clinical symptoms, or serious illnesses. Such systems include bioinformatics approaches integrated with molecular evaluation. Viruses have co-evolved different strategies to transcribe their own genetic material, by changing the host’s transcriptional machinery, even in short periods of time. The introduction of genetic alterations, particularly in RNA viruses, results in a continuous adaptive fight against the host’s immune system. We propose an in silico pipeline method for performing a comprehensive motif analysis (including motif discovery) on entire genome sequences to uncover viral sequences that may interact with host RNA binding proteins (RBPs) by interrogating the database of known RNA binding proteins, which play important roles in RNA metabolism and biological processes. Indeed, viral RNA sequences, able to bind host RBPs, may compete with cellular RNAs, altering important metabolic processes. Our findings suggest that the proposed in silico approach could be a useful and promising tool to investigate the complex and multiform clinical manifestations of viral encephalitis, and possibly identify altered metabolic pathways as targets of pharmacological treatments and innovative therapeutic protocols.

show abstract

“…Numerous ex vivo models of ZIKV infection have been described using placenta or brain tissue [43][44][45][46][47][48][49][50][51][52][53][54], but there is limited literature describing infection of other mucosal tissues [55] and the impact of viral exposure on the mucosal environment. Our ex vivo mucosal tissue explant models of ZIKV challenge for the colorectum and the FGT were adapted from the models used for HIV [56][57][58][59].…”

Section: Discussionmentioning

confidence: 99%

Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques

et al. 2022

View full text Add to dashboard Cite

Zika virus (ZIKV) cases continue to be reported, and no vaccine or specific antiviral agent has been approved for the prevention or treatment of infection. Though ZIKV is primarily transmitted by mosquitos, cases of sexual transmission and prolonged viral RNA presence in semen have been reported. In this observational study, we report the mucosal responses to sub-cutaneous and mucosal ZIKV exposure in cynomolgus macaques during acute and late chronic infection. Subcutaneous challenge induced a decrease in the growth factor VEGF in colorectal and cervicovaginal tissues 100 days post-challenge, in contrast to the observed increase in these tissues following vaginal infection. This different pattern was not observed in the uterus, where VEGF was upregulated independently of the challenge route. Vaginal challenge induced a pro-inflammatory profile in all mucosal tissues during late chronic infection. Similar responses were already observed during acute infection in a vaginal tissue explant model of ex vivo challenge. Non-productive and productive infection 100 days post-in vivo vaginal challenge induced distinct proteomic profiles which were characterized by further VEGF increase and IL-10 decrease in non-infected animals. Ex vivo challenge of mucosal explants revealed tissue-specific modulation of cytokine levels during the acute phase of infection. Mucosal cytokine profiles could represent biosignatures of persistent ZIKV infection.

show abstract

Human Testicular Germ Cells, a Reservoir for Zika Virus, Lack Antiviral Response Upon Zika or Poly(I:C) Exposure

Cited by 9 publications

References 44 publications

Antiviral Defence Mechanisms during Early Mammalian Development

Antiviral Defence Mechanisms during Early Mammalian Development

The Continuous Adaptive Challenge Played by Arboviruses: An In Silico Approach to Identify a Possible Interplay between Conserved Viral RNA Sequences and Host RNA Binding Proteins (RBPs)

Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques

Contact Info

Product

Resources

About