Outbreak of Zika Virus Infection, Chiapas State, Mexico, 2015, and First Confirmed Transmission by<i>Aedes aegypti</i>Mosquitoes in the Americas

Guerbois, Mathilde; Fernández‐Salas, Ildefonso; Azar, Sasha R.; Danis‐Lozano, Rogelio; Alpuche-Aranda, Celia; Leal, Grace; Garcia-Malo, Iliana R.; Díaz-González, Esteban E.; Casas-Martínez, Mauricio; Rossi, Shannan L.; Río-Galván, Samanta L. Del; Sánchez‐Casas, Rosa; Roundy, Christopher M.; Wood, Thomas G.; Widen, Steven G.; Vasilakis, Nikos; Weaver, Scott C.

doi:10.1093/infdis/jiw302

Cited by 175 publications

(159 citation statements)

References 34 publications

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“…Recent reports have shown that Aedes aegypti mosquitoes are highly competent vectors for American isolates of ZIKV (10). In addition, A. aegypti was found to be the primary vector for ZIKV in southern Mexico (11). Mouse models for ZIKV neuropathogenesis and in utero transmission have recently been reported in mice deficient in innate immune responses by using African and Asian genotype isolates (12)(13)(14)(15), though there have not been in vivo pathogenesis studies using an isolate from the American outbreak.…”

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confidence: 99%

Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone

Weger-Lucarelli

Duggal

Bullard-Feibelman

et al. 2017

J Virol

112

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Zika virus (ZIKV; family Flaviviridae, genus Flavivirus) is a rapidly expanding global pathogen that has been associated with severe clinical manifestations, including devastating neurological disease in infants. There are currently no molecular clones of a New World ZIKV available that lack significant attenuation, hindering progress toward understanding determinants of transmission and pathogenesis. Here we report the development and characterization of a novel ZIKV reverse genetics system based on a 2015 isolate from Puerto Rico (PRVABC59). We generated a two-plasmid infectious clone system from which infectious virus was rescued that replicates in human and mosquito cells with growth kinetics representative of wildtype ZIKV. Infectious clone-derived virus initiated infection and transmission rates in Aedes aegypti mosquitoes comparable to those of the primary isolate and displayed similar pathogenesis in AG129 mice. This infectious clone system provides a valuable resource to the research community to explore ZIKV molecular biology, vaccine development, antiviral development, diagnostics, vector competence, and disease pathogenesis.IMPORTANCE ZIKV is a rapidly spreading mosquito-borne pathogen that has been linked to Guillain-Barré syndrome in adults and congenital microcephaly in developing fetuses and infants. ZIKV can also be sexually transmitted. The viral molecular determinants of any of these phenotypes are not well understood. There is no reverse genetics system available for the current epidemic virus that will allow researchers to study ZIKV immunity, develop novel vaccines, or develop antiviral drugs. Here we provide a novel infectious clone system generated from a recent ZIKV isolated from a patient infected in Puerto Rico. This infectious clone produces virus with in vitro and in vivo characteristics similar to those of the primary isolate, providing a critical tool to study ZIKV infection and disease.

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confidence: 99%

Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone

Weger-Lucarelli

Duggal

Bullard-Feibelman

et al. 2017

J Virol

112

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“…Given the urgent need to increase our understanding of ZIKV, we asked whether RPLP1/2 are also required for ZIKV infection. We analyzed ZIKV isolates of the American lineage (isolate MEX_I_7) (33) and African lineage (isolate 41525) (34). To this end, we knocked down RPLP1/2 in A549 and HuH-7 cells and then infected the cells at an MOI of 1.…”

Section: Resultsmentioning

confidence: 99%

RPLP1 and RPLP2 Are Essential Flavivirus Host Factors That Promote Early Viral Protein Accumulation

Campos

Wong

Xie

et al. 2017

J Virol

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The Flavivirus genus contains several arthropod-borne viruses that pose global health threats, including dengue viruses (DENV), yellow fever virus (YFV), and Zika virus (ZIKV). In order to understand how these viruses replicate in human cells, we previously conducted genome-scale RNA interference screens to identify candidate host factors. In these screens, we identified ribosomal proteins RPLP1 and RPLP2 (RPLP1/2) to be among the most crucial putative host factors required for DENV and YFV infection. RPLP1/2 are phosphoproteins that bind the ribosome through interaction with another ribosomal protein, RPLP0, to form a structure termed the ribosomal stalk. RPLP1/2 were validated as essential host factors for DENV, YFV, and ZIKV infection in two human cell lines: A549 lung adenocarcinoma and HuH-7 hepatoma cells, and for productive DENV infection of Aedes aegypti mosquitoes. Depletion of RPLP1/2 caused moderate cell-line-specific effects on global protein synthesis, as determined by metabolic labeling. In A549 cells, global translation was increased, while in HuH-7 cells it was reduced, albeit both of these effects were modest. In contrast, RPLP1/2 knockdown strongly reduced early DENV protein accumulation, suggesting a requirement for RPLP1/2 in viral translation. Furthermore, knockdown of RPLP1/2 reduced levels of DENV structural proteins expressed from an exogenous transgene. We postulate that these ribosomal proteins are required for efficient translation elongation through the viral open reading frame. In summary, this work identifies RPLP1/2 as critical flaviviral host factors required for translation.IMPORTANCE Flaviviruses cause important diseases in humans. Examples of mosquito-transmitted flaviviruses include dengue, yellow fever and Zika viruses. Viruses require a plethora of cellular factors to infect cells, and the ribosome plays an essential role in all viral infections. The ribosome is a complex macromolecular machine composed of RNA and proteins and it is responsible for protein synthesis. We identified two specific ribosomal proteins that are strictly required for flavivirus infection of human cells and mosquitoes: RPLP1 and RPLP2 (RPLP1/2). These proteins are part of a structure known as the ribosomal stalk and help orchestrate the elongation phase of translation. We show that flaviviruses are particularly dependent on the function of RPLP1/2. Our findings suggest that ribosome composition is an important factor for virus translation and may represent a regulatory layer for translation of specific cellular mRNAs. (1)(2)(3)(4). Dengue viruses (DENV-1 to -4), the most prevalent of all arthropod-borne viruses, infect approximately 390 million people per year (1); yellow fever virus (YFV), which causes life-threatening disease (5) has reemerged this year in Africa (6); Zika virus (ZIKV) is currently responsible for a pandemic in the Americas that has caused grave concern because of associations with birth defects and Guillain-Barré syndrome (3). KEYWORDS flavivirus, ribosomal proteins, tran...

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“…For example, mosquitoes carry other insect-specific viruses including flaviviruses, which could easily lead to misleading conclusions about the presence of ZIKV using microscopy and even immunofluorescence labelling approaches. Moreover, natural infection in domestic Culex mosquitoes have never been found nor convincingly demonstrated in surveys conducted in ZIKV endemic and epidemic areas [12,13,62,63].Although mosquitoes of the Cx. pipiens complex are known spreaders of infectious agents including arboviruses, the flavivirus St Louis encephalitis virus or the alphavirus Sindbis virus [27,28], we suggest that this is not the case for ZIKV which belongs to the Spondweni serogroup with Spondweni virus, and both flaviviruses are transmitted by Aedes spp.…”

mentioning

confidence: 99%

“…An enzootic cycle limited to Africa and Asia with occasional spillover events has been described [10,11]. In the current outbreak in the Americas, ZIKV is believed to be mainly transmitted by the human-biting mosquito Aedes aegypti [12,13]. Whether a similar enzootic cycle in the Americas can be established is not known and it has been suggested that such a process would make eradication efforts 'practically impossible' [14].…”

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confidence: 99%

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confidence: 99%

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Culex quinquefasciatus mosquitoes do not support replication of Zika virus

Lourenço‐de‐Oliveira

Marques

Sreenu

et al. 2018

Journal of General Virology

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The rapid spread of Zika virus (ZIKV) in the Americas raised many questions about the role of Culex quinquefasciatus mosquitoes in transmission, in addition to the key role played by the vector Aedes aegypti. Here we analysed the competence of Cx. quinquefasciatus (with or without Wolbachia endosymbionts) for a ZIKV isolate. We also examined the induction of RNA interference pathways after viral challenge and the production of small virus-derived RNAs. We did not observe any infection nor such small virus-derived RNAs, regardless of the presence or absence of Wolbachia. Thus, Cx. quinquefasciatus does not support ZIKV replication and Wolbachia is not involved in producing this phenotype. In short, these mosquitoes are very unlikely to play a role in transmission of ZIKV. Micronesia and then in French Polynesia in 2013-2014, and after affecting most of the South Pacific islands, the virus was eventually detected in the Americas in 2015 [1][2][3][4]. The increased number of infections in humans included cases with unusually severe symptoms such as Guillain-Barr e syndrome and developmental abnormalities in newborns that are now described as congenital Zika syndrome [5][6][7][8]. As there are currently no licensed vaccines or specific therapies, the only way to interrupt ZIKV transmission is by controlling mosquito populations [9]. An enzootic cycle limited to Africa and Asia with occasional spillover events has been described [10,11]. In the current outbreak in the Americas, ZIKV is believed to be mainly transmitted by the human-biting mosquito Aedes aegypti [12,13]. Whether a similar enzootic cycle in the Americas can be established is not known and it has been suggested that such a process would make eradication efforts 'practically impossible' [14]. Experimental infections with the epidemic ZIKV genotypes demonstrated that populations of Ae. aegypti and Ae. albopictus mosquitoes, which are associated with a risk of local transmission [15] as well other aedine species were heterogeneously and weakly competent for transmission [16][17][18][19][20][21][22][23][24][25]. Therefore, the potential role of other anthropophilic mosquitoes in the ZIKV outbreak raised a question which took time to be addressed [26]. Culex quinquefasciatus Say is an opportunistic blood feeder predominant in urban settings throughout the tropics where it is frequently the most annoying biting pest to humans [27]. This night-active mosquito is also the vector of many pathogens including arboviruses such as West Nile and St. Louis encephalitis viruses [28], which belong to the genus Flavivirus of the family Flaviviridae and are related to ZIKV. Both Cx. quinquefasciatus and Culex pipiens (from temperate regions) mosquitoes of the Cx. pipiens complex were not able to experimentally transmit ZIKV and no viral particles were detected in mosquito saliva up to 21 days after exposure to an infectious blood meal [17-20, 25, 29-36], though different results were recorded with other Cx. quinquefasciatus strains [37,38]. Even after injection o...

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Outbreak of Zika Virus Infection, Chiapas State, Mexico, 2015, and First Confirmed Transmission byAedes aegyptiMosquitoes in the Americas

Cited by 175 publications

References 34 publications

Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone

Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone

RPLP1 and RPLP2 Are Essential Flavivirus Host Factors That Promote Early Viral Protein Accumulation

Culex quinquefasciatus mosquitoes do not support replication of Zika virus

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