Zika Virus Disease Cases — 50 States and the District of Columbia, January 1–July 31, 2016

Walker, William L.; Lindsey, Nicole P.; Lehman, Jennifer; Krow-Lucal, Elisabeth; Rabe, Ingrid B.; Hills, Susan L.; Martin, Stacey W.; Fischer, Marc; Staples, J. Erin

doi:10.15585/mmwr.mm6536e5

Cited by 44 publications

(44 citation statements)

References 8 publications

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“…ZIKV outbreaks have been recorded in the United States and Hawaii has encountered few cases of travel related ZIKV [3–5]. Using archived blood samples, we recently demonstrated ZIKV IgM and IgG antibodies in six mothers who gave birth to babies with microcephaly in Hawaii between 2009 and 2012 [6].…”

Section: Introductionmentioning

confidence: 99%

A guinea pig model of Zika virus infection

Kumar

Krause

Azouz

et al. 2017

Virol J

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BackgroundAnimal models are critical to understand disease and to develop countermeasures for the ongoing epidemic of Zika virus (ZIKV). Here we report that immunocompetent guinea pigs are susceptible to infection by a contemporary American strain of ZIKV.MethodsDunkin-Hartley guinea pigs were inoculated with 106 plaque-forming units of ZIKV via subcutaneous route and clinical signs were observed. Viremia, viral load in the tissues, anti-ZIKV neutralizing antibody titer, and protein levels of multiple cytokine and chemokines were analyzed using qRT-PCR, plaque assay, plaque reduction neutralization test (PRNT) and multiplex immunoassay.ResultsUpon subcutaneous inoculation with PRVABC59 strain of ZIKV, guinea pigs demonstrated clinical signs of infection characterized by fever, lethargy, hunched back, ruffled fur, and decrease in mobility. ZIKV was detected in the whole blood and serum using qRT-PCR and plaque assay. Anti-ZIKV neutralizing antibody was detected in the infected animals using PRNT. ZIKV infection resulted in a dramatic increase in protein levels of multiple cytokines, chemokines and growth factors in the serum. ZIKV replication was observed in spleen and brain, with the highest viral load in the brain. This data demonstrate that after subcutaneous inoculation, the contemporary ZIKV strain is neurotropic in guinea pigs.ConclusionThe guinea pig model described here recapitulates various clinical features and viral kinetics observed in ZIKV-infected patients, and therefore may serve as a model to study ZIKV pathogenesis, including pregnancy outcomes and for evaluation of vaccines and therapeutics.

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Section: Introductionmentioning

confidence: 99%

A guinea pig model of Zika virus infection

Kumar

Krause

Azouz

et al. 2017

Virol J

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“…More than 2 million suspected cases have been reported (1), and ZIKV is now considered a major public health threat by the World Health Organization (WHO). Whereas the bite of an infected Aedes aegypti mosquito is the main cause of ZIKV transmission, direct human-to-human transmissions by sexual contacts have also been reported (2).…”

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confidence: 99%

Zika Virus Methyltransferase: Structure and Functions for Drug Design Perspectives

Coutard

Barral

Lichière

et al. 2017

J Virol

124

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The Flavivirus Zika virus (ZIKV) is the causal agent of neurological disorders like microcephaly in newborns or Guillain-Barre syndrome. Its NS5 protein embeds a methyltransferase (MTase) domain involved in the formation of the viral mRNA cap. We investigated the structural and functional properties of the ZIKV MTase. We show that the ZIKV MTase can methylate RNA cap structures at the N-7 position of the cap, and at the 2=-O position on the ribose of the first nucleotide, yielding a cap-1 structure. In addition, the ZIKV MTase methylates the ribose 2=-O position of internal adenosines of RNA substrates. The crystal structure of the ZIKV MTase determined at a 2.01-Å resolution reveals a crystallographic homodimer. One chain is bound to the methyl donor (S-adenosyl-L-methionine [SAM]) and shows a high structural similarity to the dengue virus (DENV) MTase. The second chain lacks SAM and displays conformational changes in the ␣X ␣-helix contributing to the SAM and RNA binding. These conformational modifications reveal a possible molecular mechanism of the enzymatic turnover involving a conserved Ser/Arg motif. In the second chain, the SAM binding site accommodates a sulfate close to a glycerol that could serve as a basis for structure-based drug design. In addition, compounds known to inhibit the DENV MTase show similar inhibition potency on the ZIKV MTase. Altogether these results contribute to a better understanding of the ZIKV MTase, a central player in viral replication and host innate immune response, and lay the basis for the development of potential antiviral drugs. IMPORTANCE The Zika virus (ZIKV) is associated with microcephaly in newborns,and other neurological disorders such as Guillain-Barre syndrome. It is urgent to develop antiviral strategies inhibiting the viral replication. The ZIKV NS5 embeds a methyltransferase involved in the viral mRNA capping process, which is essential for viral replication and control of virus detection by innate immune mechanisms. We demonstrate that the ZIKV methyltransferase methylates the mRNA cap and adenosines located in RNA sequences. The structure of ZIKV methyltransferase shows high structural similarities to the dengue virus methyltransferase, but conformational specificities highlight the role of a conserved Ser/Arg motif, which participates in RNA and SAM recognition during the reaction turnover. In addition, the SAM binding site accommodates a sulfate and a glycerol, offering structural information to initiate structure-based drug design. Altogether, these results contribute to a better understanding of the Flavivirus methyltransferases, which are central players in the virus replication.KEYWORDS methyltransferase, RNA processing, Zika virus, flavivirus, protein structure-function

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“…Transmission through sex is also listed but without any contextual information about the frequency of reported cases, unlike the entries for transmission through blood transfusion or laboratory exposure [6]. The CDC surveillance report shows that only 23 out of 2,382 (1%) reported cases resulted from sexual contact with a traveller to an affected area [7]. …”

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confidence: 99%