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Article: Comprendre les mécanismes de transmission sexuelle des virus : apports et limites des modèles in vitro.

Frouard, Julie / Le Tortorec, Anna / Dejucq-Rainsford, Nathalie

2020 Volume 22, Issue 1, Page(s) 9–26

Abstract: Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of ... ...

Title translation	In vitro models for deciphering the mechanisms underlying the sexual transmission of viruses at the mucosal level.
Abstract	Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of entry into the organism of viruses transmitted through sexual intercourse is a necessary prerequisite to the design of treatments to block those infections, in vitro modeling of the transmission is essential. The aim of this review is to present the models and methodologies available for in vitro study of interactions between viruses and mucosal tissue and for preclinical evaluation of antiviral compounds, and to point out their advantages and limitations according to the question being studied.
Language	French
Publishing date	2020-10-28
Publishing country	France
Document type	Journal Article
ZDB-ID	2118387-9
ISSN	1950-6961 ; 1267-8694
ISSN (online)	1950-6961
ISSN	1267-8694
DOI	10.1684/vir.2018.0720
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: In vitro models for deciphering the mechanisms underlying the sexual transmission of viruses at the mucosal level.

Frouard, Julie / Le Tortorec, Anna / Dejucq-Rainsford, Nathalie

Virology

2018 Volume 515, Page(s) 1–10

Abstract	Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of entry into the organism of viruses transmitted through sexual intercourse is a necessary prerequisite to the design of treatments to block those infections, in vitro modeling of the transmission is essential. The aim of this review is to present the models and methodologies available for the in vitro study of the interactions between viruses and mucosal tissue and for the preclinical evaluation of antiviral compounds, and to point out their advantages and limitations according to the question being studied.
MeSH term(s)	Colon/virology ; Culture Techniques ; Epithelial Cells/virology ; Genitalia/virology ; Humans ; Mucous Membrane/virology ; Rectum/virology ; Sexually Transmitted Diseases, Viral/transmission ; Sexually Transmitted Diseases, Viral/virology ; Virus Internalization ; Viruses
Language	English
Publishing date	2018
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2017.11.023
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Article ; Online: SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects

Mahé, Dominique / Bourgeau, Salomé / da Silva, Janaina / Schlederer, Julie / Satie, Anne-Pascale / Kuassivi, Nadège / Mathieu, Romain / Guillou, Yves-Marie / Le Tortorec, Anna / Guivel-Benhassine, Florence / Schwartz, Olivier / Plotton, Ingrid / Dejucq-Rainsford, Nathalie

Journal of virology

2023 Volume 97, Issue 10, Page(s) e0110423

Abstract: Importance: SARS-CoV-2 is a new virus responsible for the Covid-19 pandemic. Although SARS-CoV-2 primarily affects the lungs, other organs are infected. Alterations of testosteronemia and spermatozoa motility in infected men have raised questions about ... ...

Abstract	Importance: SARS-CoV-2 is a new virus responsible for the Covid-19 pandemic. Although SARS-CoV-2 primarily affects the lungs, other organs are infected. Alterations of testosteronemia and spermatozoa motility in infected men have raised questions about testicular infection, along with high level in the testis of ACE2, the main receptor used by SARS-CoV-2 to enter host cells. Using an organotypic culture of human testis, we found that SARS-CoV-2 replicated with slow kinetics in the testis. The virus first targeted testosterone-producing Leydig cells and then germ-cell nursing Sertoli cells. After a peak followed by the upregulation of antiviral effectors, viral replication in the testis decreased and did not induce any major damage to the tissue. Altogether, our data show that SARS-CoV-2 replicates in the human testis to a limited extent and suggest that testicular damages in infected patients are more likely to result from systemic infection and inflammation than from viral replication in the testis.
MeSH term(s)	Humans ; Male ; SARS-CoV-2/physiology ; Testis/virology ; Virus Replication ; Leydig Cells/virology ; Sertoli Cells/virology
Language	English
Publishing date	2023-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01104-23
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Article ; Online: 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, Florence / Mathieu, Romain / Rebours, Valérie / Le Tortorec, Anna / Dejucq-Rainsford, Nathalie

Frontiers in immunology

2022 Volume 13, Page(s) 909341

Abstract: Zika virus (ZIKV) is an emerging teratogenic arbovirus that persists in semen and is sexually transmitted. We previously demonstrated that ZIKV infects the human testis and persists in testicular germ cells (TGCs) for several months after patients' ... ...

Abstract	Zika virus (ZIKV) is an emerging teratogenic arbovirus that persists in semen and is sexually transmitted. We previously demonstrated that ZIKV infects the human testis and persists in testicular germ cells (TGCs) for several months after patients' recovery. To decipher the mechanisms underlying prolonged ZIKV replication in TGCs, we compared the innate immune response of human testis explants and isolated TGCs to ZIKV and to Poly(I:C), a viral RNA analog. Our results demonstrate the weak innate responses of human testis to both ZIKV and Poly(I:C) as compared with other tissues or species. TGCs failed to up-regulate antiviral effectors and type I IFN upon ZIKV or Poly(I:C) stimulation, which might be due to a tight control of PRR signaling, as evidenced by the absence of activation of the downstream effector IRF3 and elevated expression of repressors. Importantly, exogenous IFNβ boosted the innate immunity of TGCs and inhibited ZIKV replication in the testis
MeSH term(s)	Antiviral Agents/pharmacology ; Germ Cells/metabolism ; Humans ; Male ; Poly I-C/metabolism ; Poly I-C/pharmacology ; Testis/metabolism ; Zika Virus ; Zika Virus Infection
Chemical Substances	Antiviral Agents ; Poly I-C (O84C90HH2L)
Language	English
Publishing date	2022-06-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.909341
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Article: Human Ubiquitin-Specific Peptidase 18 Is Regulated by microRNAs

Rubino, Erminia / Cruciani, Melania / Tchitchek, Nicolas / Le Tortorec, Anna / Rolland, Antoine D / Veli, Önay / Vallet, Leslie / Gaggi, Giulia / Michel, Frédérique / Dejucq-Rainsford, Nathalie / Pellegrini, Sandra

Frontiers in genetics

2021 Volume 11, Page(s) 627007

Abstract: Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a ... ...

Abstract	Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of IFN-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here, we identified microRNAs (miRNAs) that efficiently target
Language	English
Publishing date	2021-02-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2020.627007
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Article ; Online: From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract.

Le Tortorec, Anna / Matusali, Giulia / Mahé, Dominique / Aubry, Florence / Mazaud-Guittot, Séverine / Houzet, Laurent / Dejucq-Rainsford, Nathalie

Physiological reviews

2020 Volume 100, Issue 3, Page(s) 1349–1414

Abstract: The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the ... ...

Abstract	The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the embryo/fetal development abnormalities, and sexual dissemination of major viral pathogens such as human immunodeficiency virus (HIV) and hepatitis B virus. Lately, two emerging viruses, Zika and Ebola, have additionally revealed that the human MGT can constitute a reservoir for viruses cleared from peripheral circulation by the immune system, leading to their sexual transmission by cured men. This represents a concern for future epidemics and further underlines the need for a better understanding of the interplay between viruses and the MGT. We review here how viruses, from ancient viruses that integrated the germline during evolution through old viruses (e.g., papillomaviruses originating from Neanderthals) and more modern sexually transmitted infections (e.g., simian zoonotic HIV) to emerging viruses (e.g., Ebola and Zika) take advantage of genital tract colonization for horizontal dissemination, viral persistence, vertical transmission, and endogenization. The MGT immune responses to viruses and the impact of these infections are discussed. We summarize the latest data regarding the sources of viruses in semen and the complex role of this body fluid in sexual transmission. Finally, we introduce key animal findings that are relevant for our understanding of viral infection and persistence in the human MGT and suggest future research directions.
MeSH term(s)	Communicable Diseases, Emerging/virology ; Genitalia, Male/virology ; Humans ; Male ; Virus Diseases/pathology ; Virus Diseases/virology
Keywords	covid19
Language	English
Publishing date	2020-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00021.2019
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Article: In vitro models for deciphering the mechanisms underlying the sexual transmission of viruses at the mucosal level

Frouard, Julie / Le Tortorec, Anna / Dejucq-Rainsford, Nathalie

Virology. 2018 Feb., v. 515

2018

Abstract	Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of entry into the organism of viruses transmitted through sexual intercourse is a necessary prerequisite to the design of treatments to block those infections, in vitro modeling of the transmission is essential. The aim of this review is to present the models and methodologies available for the in vitro study of the interactions between viruses and mucosal tissue and for the preclinical evaluation of antiviral compounds, and to point out their advantages and limitations according to the question being studied.
Keywords	Bovine viral diarrhea virus 1 ; antiviral agents ; in vitro studies ; models ; mucosa ; secretion ; virology ; virus transmission ; viruses
Language	English
Dates of publication	2018-02
Size	p. 1-10.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2017.11.023
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Antiviral inhibition of enveloped virus release by tetherin/BST-2: action and counteraction.

Le Tortorec, Anna / Willey, Suzanne / Neil, Stuart J D

Viruses

2011 Volume 3, Issue 5, Page(s) 520–540

Abstract: Tetherin (BST2/CD317) has been recently recognized as a potent interferon-induced antiviral molecule that inhibits the release of diverse mammalian enveloped virus particles from infected cells. By targeting an immutable structure common to all these ... ...

Abstract	Tetherin (BST2/CD317) has been recently recognized as a potent interferon-induced antiviral molecule that inhibits the release of diverse mammalian enveloped virus particles from infected cells. By targeting an immutable structure common to all these viruses, the virion membrane, evasion of this antiviral mechanism has necessitated the development of specific countermeasures that directly inhibit tetherin activity. Here we review our current understanding of the molecular basis of tetherin's mode of action, the viral countermeasures that antagonize it, and how virus/tetherin interactions may affect viral transmission and pathogenicity.
MeSH term(s)	Antigens, CD/genetics ; Antigens, CD/metabolism ; Down-Regulation ; GPI-Linked Proteins/antagonists & inhibitors ; GPI-Linked Proteins/genetics ; GPI-Linked Proteins/metabolism ; HIV/genetics ; HIV/physiology ; HIV Infections/genetics ; HIV Infections/metabolism ; HIV Infections/virology ; Humans ; Protein Binding ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Release
Chemical Substances	Antigens, CD ; BST2 protein, human ; GPI-Linked Proteins ; Viral Proteins
Language	English
Publishing date	2011-05-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v3050520
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Le tractus génital masculin : un refuge pour le VIH ?

Le Tortorec, Anna / Dejucq-Rainsford, Nathalie

Medecine sciences : M/S

2010 Volume 26, Issue 10, Page(s) 861–868

Abstract: Despite semen being the main vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the virus in this bodily fluid remains unknown. Of particular significance is the persistence of virus release in the semen of a subset of ... ...

Title translation	Infection of semen-producing organs by HIV and role in virus dissemination.
Abstract	Despite semen being the main vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the virus in this bodily fluid remains unknown. Of particular significance is the persistence of virus release in the semen of a subset of HIV-infected men under antiretroviral therapy, who otherwise show an undetectable blood viral load. It is therefore considered critical to identify the sources of virus shedding in semen for the more efficient control of HIV transmission. Our recent findings indicate HIV infection of several semen-producing organs, including the testis (which represents a pharmacological sanctuary for several antiretroviral drugs). This reinforces phylogenetic observations suggesting that the free viral particles and infected cells contaminating semen are produced within the male genital tract. The fact that HIV replicates within the male genital organs raises several questions: Is one or several of the male genital tract organs responsible for the persistence of HIV in semen despite efficient antiviral therapies? What is the nature of HIV interactions with spermatozoa and testicular germ cells? Recent results established that semen from HIV negative men modifies HIV infectivity: does the seminal fluid from HIV+ men enhance or inhibit the efficiency of HIV sexual transmission?
MeSH term(s)	Anti-HIV Agents/therapeutic use ; Genitalia, Male/virology ; HIV/isolation & purification ; HIV Infections/drug therapy ; HIV Infections/physiopathology ; HIV Infections/transmission ; HIV Seronegativity ; Humans ; Male ; Semen/physiology ; Semen/virology ; Spermatozoa/virology ; Testis/virology
Chemical Substances	Anti-HIV Agents
Language	French
Publishing date	2010-10
Publishing country	France
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/20102610861
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Article: Alder pollen in Finland ripens after a short exposure to warm days in early spring, showing biennial variation in the onset of pollen ripening

Linkosalo, Tapio / Anna-Mari Pessi / Annika Saarto / Eric Le Tortorec / Marje Prank

Agricultural and forest meteorology. 2017 Dec. 15, v. 247

2017

Abstract: We developed a temperature sum model to predict the daily pollen release of alder, based on pollen data collected with pollen traps at seven locations in Finland over the years 2000–2014. We estimated the model parameters by minimizing the sum of squared ...

Abstract	We developed a temperature sum model to predict the daily pollen release of alder, based on pollen data collected with pollen traps at seven locations in Finland over the years 2000–2014. We estimated the model parameters by minimizing the sum of squared errors (SSE) of the model, with weights that put more weight on binary recognition of daily presence or absence of pollen. The model results suggest that alder pollen ripens after a couple of warm days in February, while the whole pollen release period typically takes up to 4 weeks. We tested the model residuals against air humidity, precipitation and wind speed, but adding these meteorological features did not improve the model prediction capacity.Our model was able to predict the onset of pollen season with similar accuracy as models describing only the start of the pollen release period (average prediction error 8.3, median 5.0days), while for the end of the pollen release period the accuracy of our predictions was not as good. We split the pollen data into odd and even years, and fitted our model separately to each half. Difference in the parameter values suggests a biennial behavior in the onset of pollen ripening, with almost two weeks of difference in the modeled starting date of the pollen development. Monte Carlo resampling of the observation data confirmed that the difference is not just a random anomaly in the data.
Keywords	air ; data collection ; heat sums ; humidity ; models ; pollen ; prediction ; ripening ; spore traps ; spring ; wind speed ; Finland
Language	English
Dates of publication	2017-1215
Size	p. 408-413.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	409905-9
ISSN	0168-1923
ISSN	0168-1923
DOI	10.1016/j.agrformet.2017.08.030
Database	NAL-Catalogue (AGRICOLA)

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