Dataset Information

Characterization of large and small-plaque variants in the Zika virus clinical isolate ZIKV/Hu/S36/Chiba/2016.

ABSTRACT: An Asian/American lineage Zika virus (ZIKV) strain ZIKV/Hu/S36/Chiba/2016 formed 2 types in plaque size, large and small. Genomic analysis of the plaque-forming clones obtained from the isolate indicated that the clones forming small plaques commonly had an adenine nucleotide at position 796 (230Gln in the amino acid sequence), while clones forming large plaques had a guanine nucleotide (230Arg) at the same position, suggesting that this position was associated with the difference in plaque size. Growth kinetics of a large-plaque clone was faster than that of a small-plaque clone in Vero cells. Recombinant ZIKV G796A/rZIKV-MR766, which carries a missense G796A mutation, was produced using an infectious molecular clone of the ZIKV MR766 strain rZIKV-MR766/pMW119-CMVP. The plaque size of the G796A mutant was significantly smaller than that of the parental strain. The G796A mutation clearly reduced the growth rate of the parental virus in Vero cells. Furthermore, the G796A mutation also decreased the virulence of the MR766 strain in IFNAR1 knockout mice. These results indicate that the amino acid variation at position 230 in the viral polyprotein, which is located in the M protein sequence, is a molecular determinant for plaque morphology, growth property, and virulence in mice of ZIKV.

SUBMITTER: Kato F

PROVIDER: S-EPMC5701032 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Characterization of large and small-plaque variants in the Zika virus clinical isolate ZIKV/Hu/S36/Chiba/2016.

Kato Fumihiro F Tajima Shigeru S Nakayama Eri E Kawai Yasuhiro Y Taniguchi Satoshi S Shibasaki Kenichi K Taira Masakatsu M Maeki Takahiro T Lim Chang Kweng CK Takasaki Tomohiko T Saijo Masayuki M

Scientific reports 20171123 1

An Asian/American lineage Zika virus (ZIKV) strain ZIKV/Hu/S36/Chiba/2016 formed 2 types in plaque size, large and small. Genomic analysis of the plaque-forming clones obtained from the isolate indicated that the clones forming small plaques commonly had an adenine nucleotide at position 796 (230<sup>Gln</sup> in the amino acid sequence), while clones forming large plaques had a guanine nucleotide (230<sup>Arg</sup>) at the same position, suggesting that this position was associated with the dif ...[more]

PMID: 29170504

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Project description:BackgroundLocal mosquito-borne Zika virus (ZIKV) transmission has been reported in two counties in the contiguous United States (US), prompting the issuance of travel, prevention, and testing guidance across the contiguous US. Large uncertainty, however, surrounds the quantification of the actual risk of ZIKV introduction and autochthonous transmission across different areas of the US.MethodsWe present a framework for the projection of ZIKV autochthonous transmission in the contiguous US during the 2015-2016 epidemic using a data-driven stochastic and spatial epidemic model accounting for seasonal, environmental, and detailed population data. The model generates an ensemble of travel-related case counts and simulates their potential to have triggered local transmission at the individual level in the 2015-2016 ZIKV epidemic.ResultsWe estimate the risk of ZIKV introduction and local transmission at the county level and at the 0.025° × 0.025° cell level across the contiguous US. We provide a risk measure based on the probability of observing local transmission in a specific location during a ZIKV epidemic modeled after the epidemic observed during the years 2015-2016. The high spatial and temporal resolution of the model allows us to generate statistical estimates of the number of ZIKV introductions leading to local transmission in each location. We find that the risk was spatially heterogeneously distributed and concentrated in a few specific areas that account for less than 1% of the contiguous US population. Locations in Texas and Florida that have actually experienced local ZIKV transmission were among the places at highest risk according to our results. We also provide an analysis of the key determinants for local transmission and identify the key introduction routes and their contributions to ZIKV transmission in the contiguous US.ConclusionsThis framework provides quantitative risk estimates, fully captures the stochasticity of ZIKV introduction events, and is not biased by the under-ascertainment of cases due to asymptomatic cases. It provides general information on key risk determinants and data with potential uses in defining public health recommendations and guidance about ZIKV risk in the US.

Project description:Zika virus (ZIKV) infection is now firmly linked to congenital Zika syndrome (CZS), including fetal microcephaly. While Aedes species of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse, and nonhuman primate (NHP) semen. It is critical to establish NHP models of the vertical transfer of ZIKV that recapitulate human pathogenesis. We hypothesized that vaginal deposition of ZIKV-infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Epidemiological studies suggest an increased rate of CZS in the Americas compared to the original link to CZS in French Polynesia; therefore, we also compared the French Polynesian (FP) ZIKV isolate to the Puerto Rican (PR) isolate. Timed-pregnant baboons (n = 6) were inoculated via vaginal deposition of baboon semen containing 106 focus-forming units (FFU) of ZIKV (n = 3 for FP isolate H/PF/2013; n = 3 for PR isolate PRVABC59) at midgestation (86 to 95 days of gestation [dG]; term, 183 dG) on day 0 (all dams) and then at 7-day intervals through 3 weeks. Maternal blood, saliva, and cervicovaginal wash (CVW) samples were obtained. Animals were euthanized at 28 days (n = 5) or 39 days (n = 1) after the initial inoculation, and maternal/fetal tissues were collected. Viremia was achieved in 3/3 FP ZIKV-infected dams and 2/3 PR ZIKV-infected dams. ZIKV RNA was detected in CVW samples of 5/6 dams. ZIKV RNA was detected in lymph nodes but not the ovaries, uterus, cervix, or vagina in FP isolate-infected dams. ZIKV RNA was detected in lymph nodes (3/3), uterus (2/3), and vagina (2/3) in PR isolate-infected dams. Placenta, amniotic fluid, and fetal tissues were ZIKV RNA negative in the FP isolate-infected dams, whereas 2/3 PR isolate-infected dam placentas were ZIKV RNA positive. We conclude that ZIKV-infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of widespread dissemination to tissues, including reproductive tissues and placenta, than the FP isolate.IMPORTANCE Zika virus remains a worldwide health threat, with outbreaks still occurring in the Americas. While mosquitos are the primary vector for the spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to an uninfected partner. While sexual transmission has been documented in humans, and male-to-female transmission has been reported in mice, ours is the first study in nonhuman primates to demonstrate infection via vaginal deposition of Zika virus-infected semen. The latter is important since a recent publication indicated that human semen inhibited, in a laboratory setting, Zika virus infection of reproductive tissues. We also found that compared to the French Polynesian isolate, the Puerto Rican Zika virus isolate led to greater spread throughout the body, particularly in reproductive tissues. The American isolates of Zika virus appear to have acquired mutations that increase their efficacy.

Project description:BackgroundZika virus (ZIKV) has been identified in several body fluids of infected individuals. In most cases, it remained detected in blood from few days to 1 week after the onset of symptoms, and can persist longer in urine and in semen. ZIKV infection can have dramatic consequences such as microcephaly and Guillain-Barré syndrome. ZIKV sexual transmission has been documented. A better understanding of ZIKV presence and persistence across biologic compartments is needed to devise rational measures to prevent its transmission.MethodsThis observational cohort study will recruit non-pregnant participants aged 18 years and above with confirmed ZIKV infection [positive reverse transcriptase-polymerase chain reaction (RT-PCR) test in blood and/or urine]: symptomatic men and women in ZIKV infection acute phase, and their symptomatic or asymptomatic household/sexual infected contacts. Specimens of blood, urine, semen, vaginal secretion/menstrual blood, rectal swab, oral fluids, tears, sweat, urine and breast milk (if applicable) will be collected at pre-established intervals and tested for ZIKV RNA presence by RT-PCR, other co-infection (dengue, Chikungunya, HIV, hepatitis B and C, syphilis), antibody response (including immunoglobulins M and G), plaque reduction neutralization test (if simultaneously positive for ZIKV and dengue), and ZIKV culture and RNA sequencing. Data on socio-demographic characteristics and comorbidities will be collected in parallel. Participants will be followed up for 12 months.DiscussionThis prolonged longitudinal follow-up of ZIKV infected persons with regular biologic testing and data collection will offer a unique opportunity to investigate the presence and persistence of ZIKV in various biologic compartments, their clinical and immunological correlates as well as the possibility of ZIKV reactivation/reinfection over time. This valuable information will substantially contribute to the body of knowledge on ZIKV infection and serve as a base for the development of more effective recommendation on the prevention of ZIKV transmission.Trial registrationNCT03106714 . Registration Date: April, 7, 2017.

Dataset Information

Characterization of large and small-plaque variants in the Zika virus clinical isolate ZIKV/Hu/S36/Chiba/2016.

Publications

Characterization of large and small-plaque variants in the Zika virus clinical isolate ZIKV/Hu/S36/Chiba/2016.

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