Showing papers by "Van-Mai Cao-Lormeau published in 2015"

Potential Sexual Transmission of Zika Virus

Abstract: In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.

Biology of Zika Virus Infection in Human Skin Cells

Abstract: Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the Aedes genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus. IMPORTANCE Zika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune cells, including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells, were all found to be permissive to ZIKV infection. The results also show a major role for the phosphatidylserine receptor AXL as a ZIKV entry receptor and for cellular autophagy in enhancing ZIKV replication in permissive cells. ZIKV replication leads to activation of an antiviral innate immune response and the production of type I interferons in infected cells. Taken together, these results provide the first general insights into the interaction between ZIKV and its mammalian host.

Chikungunya outbreak, French Polynesia, 2014.

Abstract: To the Editor: Chikungunya virus (CHIKV), an arthropod-borne virus (arbovirus) of the family Togaviridae, genus Alphavirus, is transmitted by mosquitoes of the Aedes genus, especially Ae. aegypti and Ae. albopictus (1). The main clinical manifestations of CHIKV infections are sudden high fever, headache, back pain, myalgia, arthralgia affecting mainly the extremities, and rash. CHIKV emerged in the Pacific region in New Caledonia in March 2011. Additional outbreaks occurred in Papua New Guinea in June 2012; Yap State (Federated States of Micronesia) in August 2013; Tonga in April 2014; and American Samoa, Samoa, and Tokelau in July 2014 (2). Phylogenetic analysis of CHIKV strains showed the existence of 3 lineages: West African, Asian, and East/Central/South African (1). French Polynesia is a French territory in the South Pacific, with 270,000 inhabitants living on 5 archipelagoes. Arboviruses are a common cause of outbreaks in French Polynesia: the last dengue virus (DENV) outbreaks caused by DENV-1 and DENV-3 occurred in 2013 (3), and DENV-1 still circulates. French Polynesia also experienced the largest Zika virus (ZIKV) outbreak ever reported during October 2013–April 2014 (4). In May 2014, CHIKV infection was detected for the first time in French Polynesia in a traveler returning from Guadeloupe, (5) where a chikungunya outbreak was ongoing (6). In late September 2014, an increasing number of patients with fever and rash who tested negative for DENV and ZIKV by real-time reverse transcription PCR (RT-PCR) were recorded by the French Polynesia Department of Health on the south coast of Tahiti, French Polynesia’s main island. Serum samples collected from 19 of these patients were tested for CHIKV by RT-PCR using previously reported primers and a probe (7). Seven of the 19 (37%) were positive; all 7 were autochthonous. The first specimen that tested positive for CHIKV had been collected from a patient on September 25, and by October 25, a total of 318 patients were confirmed by RT-PCR to be infected by CHIKV. Nearly all districts of Tahiti were affected, and cases were reported on 4 of French Polynesia’s 5 archipelagoes. Partial sequencing of the CHIKV E1 gene of a strain isolated from a patient and collected on September 29 (strain PF14-290914-16, GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"KM985619","term_id":"807059694","term_text":"KM985619"}}KM985619) was performed as previously reported (8). Phylogenetic analysis showed that French Polynesia’s CHIKV strain belongs to the Asian lineage and is more closely related to a strain collected in the British Virgin Islands in 2014 (VG14/99659) and to the French Polynesian strain imported from Guadeloupe in May 2014 (PF14-270514-51impGP), with 99.9% homology, than to the strains that recently circulated in Yap State (FM13/3807), Tonga (TO14-080414-3007 and TO14-080414-3042), and New Caledonia (NC11-568) (Figure). Figure Phylogenetic analysis of chikungunya virus strain isolated in French Polynesia on September 29, 2014. The evolutionary history was inferred by using the maximum-likelihood method based on the Kimura 2-parameter model. The percentage of trees in which ... No cases of CHIKV infection were reported in French Polynesia within the 4 months after the imported case detected on May 25, 2014. Because of the active, ongoing circulation of CHIKV in the Pacific, introduction of this virus in French Polynesia was expected from other Pacific islands, especially from New Caledonia, because of extensive travel between the 2 French territories. The fact that the CHIKV strain circulating in French Polynesia is closely related to the strains currently circulating in the Caribbean suggests that the French Polynesia outbreak is a result of the introduction of CHIKV from the Caribbean rather than from another Pacific island. The delay between the current outbreak and the first infected patient detected in 2014 also suggests a new introduction rather than a circulation of the strain introduced in May. However, an undetected low-level circulation of CHIKV during the cooler and drier low transmission season, simultaneously with DENV-1 circulation, cannot be excluded. The introduction of arboviruses into French Polynesia from other French overseas territories rather than from other Pacific islands was previously reported for DENV. In 2013, DENV-3 reappeared in French Polynesia 3 months after the Solomon Islands had declared a DENV-3 outbreak. However, epidemiologic and phylogenetic investigations revealed that the DENV-3 strain that caused the outbreak in French Polynesia had been introduced by a traveler returning from French Guiana and belonged to a different genotype than the one that was circulating in the Solomon Islands (3). Several conditions are favorable to a large chikungunya outbreak in French Polynesia. First, because CHIKV has never been previously reported in French Polynesia, the entire population is thought to be immunologically naive for CHIKV infection. Second, 2 potential vectors for CHIKV are present in French Polynesia: Ae. aegypti (1) and Ae. polynesiensis mosquitoes (9). Third, in French Polynesia the hot and rainy season that lasts from October through March is conducive to the proliferation of mosquitoes. We have the experience of the French Polynesian ZIKV outbreak that started with the same favorable conditions in October 2013 and was responsible for 28,000 estimated symptomatic cases from October 2013 through April 2014 (10). This new outbreak corroborates the recent observation that the expansion of arboviruses in the Pacific is ongoing and inevitable (2).

Use of Centrifugal Filter Devices to Concentrate Dengue Virus in Mosquito per os Infection Experiments.

Abstract: Dengue virus (DENV) is an arbovirus transmitted to humans by the bite of infected Aedes mosquitoes Experimental per os infection of mosquitoes with DENV is usually a preliminary step in virus/vector studies but it requires being able to prepare artificial blood-meals with high virus titers We report here the convenient use of centrifugal filter devices to quickly concentrate DENV particles in cell-culture supernatants The median viral titer in concentrated-supernatants was 850 log10 TCID50/mL By using these DENV concentrated-supernatants to prepare infectious blood-meals in Aedes aegypti per os infection experiments, we obtained a mean mosquito-infection rate of 94% We also evaluated the use of centrifugal filter devices to recover DENV particles from non-infectious blood-meals presented to infected mosquitoes through a feeding membrane to collect their saliva