Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
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.
ISSN: 0042-6822

Droits : http://creativecommons.org/licenses/by/
hal-01663650
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01663650
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01663650/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01663650/file/Frouard%20-%20In%20vitro%20models%20for%20deciphering.pdf
DOI : 10.1016/j.virol.2017.11.023

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: Evidence of human sexual transmission during Zika virus emergence is a matter of concern, particularly in procreation, but to date, kinetics of seminal shedding and the effects of infection on human reproductive function have not been described. To investigate the effects of Zika virus infection on semen and clearance of Zika virus from semen and body fluids, we aimed to study a cohort of Zika virus-infected men. METHODS: This prospective observational study recruited men presenting with acute Zika virus infection at Pointe-à-Pitre University Hospital in Guadeloupe, French Caribbean, where a Zika virus outbreak occurred between April and November, 2016. Blood, urine, and semen were collected at days 7, 11, 20, 30, 60, 90, and 120 after symptom onset, and semen characteristics, such as total sperm count, sperm motility, vitality, and morphology, and reproductive hormone concentrations, such as testosterone, inhibin, follicle-stimulating hormone, and luteinising hormone, were assessed. At days 7, 11, and 20, semen was processed to isolate motile spermatozoa. Zika virus RNA was detected by RT-PCR using whole blood, serum, urine, seminal plasma, semen cells, and motile spermatozoa fractions. Zika virus was isolated from different sperm fractions on Vero E6 cultures. FINDINGS: 15 male volunteers (mean age 35 years [SD 5; range 25-44) with acute Zika virus infection and positive Zika virus RNA detection in blood or urine were enrolled. Total sperm count was decreased from median 119 × 10(6) spermatozoa (IQR 22-234) at day 7 to 45·2 × 10(6) (16·5-89·6) at day 30 and 70 × 10(6) (28·5-81·4) at day 60, respectively, after Zika virus infection. Inhibin values increased from 93·5 pg/mL (IQR 55-162) at day 7 to 150 pg/mL (78-209) at day 120 when total sperm count recovered. In motile spermatozoa obtained after density gradient separation, Zika virus RNA was found in three of 14 patients at day 7, four of 15 at day 11, and four of 15 at day 20, and replication-competent virus was found in the tested patient. Seminal shedding kinetics seemed heterogeneous among patients. Whole blood was the fluid most frequently positive for Zika virus RNA (62 of 92 samples) and three patients remained positive at day 120. INTERPRETATION: Semen alterations early after acute Zika virus infection might affect fertility and could be explained by virus effects on the testis and epididymis. Frequency of shedding and high viral load in semen, together with the presence of replicative virus in a motile spermatozoa fraction, can lead to Zika virus transmission during sexual contact and assisted reproduction procedures. Whole blood seems to be the best specimen for Zika virus RNA detection, diagnosis, and follow-up. FUNDING: Agence de la Biomédecine/Agence Régionale de Santé de la Guadeloupe/Inserm-REACTing.
ISSN: 0140-6736

hal-01647078
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647078
DOI : 10.1016/S1473-3099(17)30444-9
PUBMED : 28838639

Éditeur(s) : HAL CCSD Masson
Résumé : National audience
Started in 2015 in Brazil, an outbreak linked to a little known arbovirus, Zika virus spread throughout Latin America. This virus, considered until recently as responsible of only mild symptoms, made mention of previously unsuspected complications, with severe neurological manifestations in adults and malformations of the central nervous system, including microcephaly, in newborns of mother infected during the pregnancy. While the continent is more accustomed to the succession of arbovirus epidemics, suspected complications and the many unknowns keys of the latter arriving raise many public health issues. French Guiana, a French territory located in the north-east of the continent, combines both European level of resources and climate and issues specific to the Amazon region and Latin America. We discuss here the issues for 2016 Zika virus epidemic in our region, many of them are generalizable to neighboring countries.
ISSN: 0037-9085

inserm-01422054
http://www.hal.inserm.fr/inserm-01422054
http://www.hal.inserm.fr/inserm-01422054/document
http://www.hal.inserm.fr/inserm-01422054/file/2016%2C%20Epelboin%20-%20%C3%89pid%C3%A9mie%20de%20virus%20Zika%20en%20Am%C3%A9rique%20latine%20-%20quels%20enjeux%20pour%20la%20Guyane%20%281%29.pdf
DOI : 10.1007/s13149-016-0490-5

Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Zika fever is an Aedes-borne disease caused by a flavivirus (Zika virus, ZIKV, genus Flavivirus). During the past years ZIKV spread in Polynesia, South-America and the Caribbean. Most ZIKV infections are asymptomatic or result in mild febrile disease with rash and conjunctivitis. Attention was recently drawn to non-vectored ZIKV transmission, including sexual, probable blood-borne and mother-to-fetus transmission, and to severe forms such as Guillain-Barré syndrome, acute neurological infections and fetal abnormalities (including microcephaly). Many aspects of Zika fever natural history remain unknown, e.g. the proportion of asymptomatic cases and the duration of viremia. Estimating the prevalence of Zika infections is difficult because a large proportion of infected individuals do not seek medical attention and seroprevalence studies are hampered by antigenic cross-reactivity with other flaviviruses, e.g. dengue virus. Here, we present a study of ZIKV infection in blooddonors from Martinique island (French West Indies, Caribbean region), with novel epidemiological, biological and clinical information that refine the picture of Zika fever in adults.
ISSN: 0006-4971

inserm-01415646
http://www.hal.inserm.fr/inserm-01415646
http://www.hal.inserm.fr/inserm-01415646/document
http://www.hal.inserm.fr/inserm-01415646/file/2016%2C%20Gallian%20et%20al%20-%20Zika%20virus%20in%20asymptomatic%20blood%20donors%2C%20Martinique%20%281%29.pdf
DOI : 10.1182/blood-2016-09-737981

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure.
ISSN: 1553-7366

hal-00955292
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292/file/Semen_CD4_T-accepted.pdf
PUBMED : 24348253

Éditeur(s) : HAL CCSD Taylor & Francis (Routledge)
Résumé : International audience
The Maroni basin, an isolated region delineating the border between Suriname and French Guiana has been affected by the human immunodeficiency virus (HIV) epidemic 10 years after coastal French Guiana. However, the rise in HIV prevalence was sharp, exceeding 1% within 10 years. The aim of the present study is to compare, using the first quantitative data from the general population in remote villages, the knowledge, attitudes, and behaviors regarding HIV between Maroon and Amerindian populations, the two most frequent populations living along the Maroni. Data were collected in 2012 using a structured questionnaire among a random sample of 896 individuals residing in the remote villages on the Maroni river. Proportions were compared between the Maroni and the coastal general population, and between Maroon and Amerindian populations. The present study shows significant differences between territories and between communities living on the Maroni river: the multiple sexual partnerships, more common among population living on the Maroni river, were more frequently reported in Maroons than in Amerindians. Condom use was more frequently reported among men on the Maroni river than on the coast, but these findings were reversed for women. Moreover, among people living on the Maroni river, condom use was more frequently reported among Maroons than among Amerindians. Regarding genital factors that may affect transmission, penile implant seemed to have no ethnic boundaries, steam baths seemed specific to Maroon women. The present results should help to improve community-based specific interventions.
ISSN: 0954-0121

hal-01260915
https://hal.archives-ouvertes.fr/hal-01260915
https://hal.archives-ouvertes.fr/hal-01260915/document
https://hal.archives-ouvertes.fr/hal-01260915/file/2015%2C%20Van%20Melle%20-%20Knowledge%2C%20attitudes%2C%20behaviors%2C%20and%20practices%20differences%20regarding%20HIV.pdf
DOI : 10.1080/09540121.2015.1032203

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
A number of men receiving prolonged suppressive HAART still shed HIV in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with SIVmac251 submitted to HAART for 4 months, intensified over the last seven weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen, or in testis, epididymis, seminal vesicles and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens, and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of non-productively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organs infection in long term treated infected individuals. A substantial subset of men receiving prolonged suppressive HAART in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV-infected macaques treated by HAART. We demonstrated that persistent seminal shedding was not linked to poor drug penetration in semen or semen-producing prostate, seminal vesicle, epididymis and testis. We revealed that HAART decreased SIV RNA to various extents in all male genital organs, with the exception of the urethra, in which SIV RNA+ macrophages were observed despite HAART. Importantly also, HAART did not impact SIV DNA levels in the male genital organs. These results suggest that infection of male genital organs, and particularly the urethra, could be involved in the release of virus in semen during HAART.
ISSN: 0022-538X

hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/file/Detection%20of%20SIV%20in%20Semen%2C%20Urethra%2C%20and%20Male%20Reproductive%20Organs%20during%20Efficient%20Highly%20Active%20Antiretroviral%20Therapy.pdf
PUBMEDCENTRAL : PMC4442442