Paolo Marinho de Andrade Zanotto

Universidade de São Paulo

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Marielton dos Passos Cunha

Institut Pasteur

Edward C. Holmes

University of Sydney

Fernando L. Melo

Universidade de Brasília

Edison Luíz Durigon

Universidade de São Paulo

Camila Malta Romano

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Shahab Zaki Pour

Universidade de São Paulo

Atila Iamarino

Universidade de São Paulo

Carla Torres Braconi

Universidade Federal de São Paulo

Caio César de Melo Freire

Universidade Federal de São Carlos

Daniel Ferreira de Lima Neto

Ministério da Saúde

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Universidade de São Paulo

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Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Universidade Federal de São Paulo

Fundação Oswaldo Cruz

Institut Pasteur de Dakar

Instituto Butantan

Universidade Brasil

Universidade Estadual de Campinas (UNICAMP)

Beth Israel Deaconess Medical Center

Institut Pasteur

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Laboratory strains ofAedes aegyptiare Competent to Brazilian Zika virus

bioRxiv (Cold Spring Harbor Laboratory) (2016)

André Luis Costa‐da‐Silva Rafaella Sayuri Ioshino Helena R. C. Araújo Bianca Burini Kojin Paolo Marinho de Andrade Zanotto

Abstract Since the Zika outbreaks are unprecedented human threat in relation to congenital malformations and neurological/autoimmune complications as well as its high potential to spread in regions presenting the vectors, improvements in mosquito control is a top priority. Thus, Aedes aegypti laboratory strains will be fundamental to support studies in different research fields implicated on Zika-mosquito interactions which are the basis for the development of innovative control methods. In this sense, we determined the main infection aspects of the Brazilian Zika strain in reference Aedes aegypti laboratory mosquitoes. We orally exposed Rockefeller, Higgs and Rexville mosquitoes to a Brazilian ZIKV (ZIKV BR ) and qRT-PCR was applied to determine the infection and dissemination rates, and viral levels in mosquito tissues as well as in the saliva. The ZIKV BR kinetics was monitored during the infection in Rockefeller mosquitoes. Rockefeller strain was the most susceptible at 7 days post-infection but all strains presented similar infection levels at 14 days post-infection. Although variations in the saliva detection rates were observed, we confirmed that ZIKV BR was present in saliva from Rockefeller, Higgs and Rexville females at detectable levels at 14 days post-infection. The ZIKV BR kinetics in Rockefeller mosquitoes showed that the virus could be detected in the heads at 4 days post-infection but was more consistently detected late in infection. The viral levels peaked at 11 days post-infection in the mosquito bodies, remaining stable until 14 days post-infection, in contrast to the heads, where the mean viral levels only peaked at 14 days post-infection. Our study presents the first evaluation on how Brazilian Zika virus behaves in reference Aedes aegypti strains and shed light on how the infection evolves over time. Vector competence and basic hallmarks of the ZIKV BR development were revealed in laboratory mosquitoes. This study provides additional information to accelerate studies focusing on ZIKV-mosquito interactions.

Zika Virus

Mosquito control

10.1101/071654

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Citations (1)

A Zika virus-associated microcephaly case with background exposure to STORCH agents

bioRxiv (Cold Spring Harbor Laboratory) (2016)

Mauro Mitsuru Hanaoka Alexandre Fligelman Kanas Carla Torres Braconi Érica Araújo Mendes Robert Andreata‐Santos

Abstract We present a case of microcephaly associated with Zika virus (ZIKV) in a chronological, multimodal imaging approach, illustrating the hallmarks of this disease on intrauterine morphological ultrasound, transfontanelar ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). We also determined the serological e immunological status of the mother and newborn. Noticeably, there was evidence for maternal infection by ZIKV, cytomegalovirus (CMV), herpes simplex virus (HSV), dengue virus (DENV) and Toxoplasma gondii , which indicates a possible role of previous exposures to STORCH agents and possibly comorbidities in the severe fetal congenital manifestation. Author Summary Zika virus (ZIKV) is an emerging mosquito-borne arbovirus causing dengue-like symptoms. In humans the illness is characterized by malaise and cutaneous rash and absent or short-termed fever. Recently, the Brazilian Ministry of Health reported an outbreak of microcephaly in Brazil as a delayed effect of the 2014-2015 outbreak of ZIKV in the Northeast of Brazil. A 20-fold increase in the notifications of newborns with microcephaly was documented during the second semester of 2015. This increase was almost immediately found to be associated with ZIKV infections, both in Brazil and, retrospectively, in French Polynesia. Herein we report a case of microcephaly associated with ZIKV and we also present evidence of other maternal infections. Our results indicated that, both mother and microcephaly infant had immunologic status compatible with previous exposure (in the mother) by STORCH agents. These indicate a possible role of previous exposures and possibly comorbidities in the severe fetal congenital manifestation. □

Zika Virus

Microcephaly

10.1101/052340

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Citations (2)

Dengue Virus Type 3 Adaptive Changes during Epidemics in São Jose de Rio Preto, Brazil, 2006–2007

PLoS ONE (2013)

Christian Julián Villabona‐Arenas Adriano Mondini Irene Bosch Diane Schimitt Carlos Eduardo Calzavara-Silva

Global dengue virus spread in tropical and sub-tropical regions has become a major international public health concern. It is evident that DENV genetic diversity plays a significant role in the immunopathology of the disease and that the identification of polymorphisms associated with adaptive responses is important for vaccine development. The investigation of naturally occurring genomic variants may play an important role in the comprehension of different adaptive strategies used by these mutants to evade the human immune system. In order to elucidate this role we sequenced the complete polyprotein-coding region of thirty-three DENV-3 isolates to characterize variants circulating under high endemicity in the city of São José de Rio Preto, Brazil, during the onset of the 2006-07 epidemic. By inferring the evolutionary history on a local-scale and estimating rates of synonymous (dS) and nonsynonimous (dN) substitutions, we have documented at least two different introductions of DENV-3 into the city and detected 10 polymorphic codon sites under significant positive selection (dN/dS > 1) and 8 under significant purifying selection (dN/dS < 1). We found several polymorphic amino acid coding sites in the envelope (15), NS1 (17), NS2A (11), and NS5 (24) genes, which suggests that these genes may be experiencing relatively recent adaptive changes. Furthermore, some polymorphisms correlated with changes in the immunogenicity of several epitopes. Our study highlights the existence of significant and informative DENV variability at the spatio-temporal scale of an urban outbreak.

Negative selection

Synonymous substitution

10.1371/journal.pone.0063496

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Citations (53)

A deep phylogeny of viral and cellular right-hand polymerases

Infection Genetics and Evolution (2015)

Jiří Černý Barbora Černá Bolfíková Paolo Marinho de Andrade Zanotto Libor Grubhoffer Daniel Růžek

RNA polymerase I

10.1016/j.meegid.2015.09.026

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Citations (12)

The complete sequence of four major structural proteins of African horse sickness virus serotype 6: evolutionary relationships within and between the orbiviruses

Virus Research (1998)

Catherine F Williams Toru Inoue Anne-Marie Lucus Paolo Marinho de Andrade Zanotto Polly Roy

Orbivirus

African horse sickness

10.1016/s0168-1702(97)00131-7

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Citations (27)

High Rates of Molecular Evolution in Hantaviruses

Molecular Biology and Evolution (2008)

C. Ramsden Fernando L. Melo Luiz. M. Figueiredo Edward C. Holmes Paolo Marinho de Andrade Zanotto

Hantaviruses are rodent-borne Bunyaviruses that infect the Arvicolinae, Murinae, and Sigmodontinae subfamilies of Muridae. The rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10−7 nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. If substantiated, this would make the hantaviruses among the slowest evolving of all RNA viruses. However, as hantaviruses replicate with an RNA-dependent RNA polymerase, with error rates in the region of one mutation per genome replication, this low rate of nucleotide substitution is anomalous. Here, we use a Bayesian coalescent approach to estimate the rate of nucleotide substitution from serially sampled gene sequence data for hantaviruses known to infect each of the 3 rodent subfamilies: Araraquara virus (Sigmodontinae), Dobrava virus (Murinae), Puumala virus (Arvicolinae), and Tula virus (Arvicolinae). Our results reveal that hantaviruses exhibit short-term substitution rates of 10−2 to 10−4 substitutions/site/year and so are within the range exhibited by other RNA viruses. The disparity between this substitution rate and that estimated assuming rodent–hantavirus codivergence suggests that the codivergence hypothesis may need to be reevaluated.

Arvicolinae

Sigmodontinae

Viral evolution

Puumala virus

10.1093/molbev/msn093

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Citations (124)

Tempo and mode of ERV-K evolution in human and chimpanzee genomes

Archives of Virology (2006)

Camila Malta Romano Rodrigo Fernandes Ramalho Paolo Marinho de Andrade Zanotto

Endogenous retrovirus

Homo sapiens

10.1007/s00705-006-0792-1

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Citations (30)

An Arbovirus Cline across the Northern Hemisphere

Virology (1995)

Paolo Marinho de Andrade Zanotto Guozhen Gao Т.С. Грицун Margarita Marín Weiwei Jiang

Cline (biology)

Viral evolution

10.1006/viro.1995.1326

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Citations (143)

Proteomic analyses of baculovirus Anticarsia gemmatalis multiple nucleopolyhedrovirus budded and occluded virus

Journal of General Virology (2014)

Carla Torres Braconi Daniel Mendes Pereira Ardisson-Araújo Adriana Franco Paes Leme Juliana Oliveira Bianca Alves Pauletti

Baculoviruses infect insects, producing two distinct phenotypes during the viral life cycle: the budded virus (BV) and the occlusion-derived virus (ODV) for intra- and inter-host spread, respectively. Since the 1980s, several countries have been using Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) as a biological control agent against the velvet bean caterpillar, A. gemmatalis . The genome of AgMNPV isolate 2D (AgMNPV-2D) carries at least 152 potential genes, with 24 that possibly code for structural proteins. Proteomic studies have been carried out on a few baculoviruses, with six ODV and two BV proteomes completed so far. Moreover, there are limited data on virion proteins carried by AgMNPV-2D. Therefore, structural proteins of AgMNPV-2D were analysed by MALDI- quadrupole-TOF and liquid chromatography MS/MS. A total of 44 proteins were associated with the ODV and 33 with the BV of AgMNPV-2D. Although 38 structural proteins were already known, we found six new proteins in the ODV and seven new proteins carried by the AgMNPV-2D BV. Eleven cellular proteins that were found on several other enveloped viruses were also identified, which are possibly carried with the virion. These findings may provide novel insights into baculovirus biology and their host interaction. Moreover, our data may be helpful in subsequent applied studies aiming to improve AgMNPV use as a biopesticide and a biotechnology tool for gene expression or delivery.

Anticarsia gemmatalis

Proteome

10.1099/vir.0.061127-0

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Citations (24)

Usutu Virus Isolated from Rodents in Senegal

Viruses (2019)

Moussa Moïse Diagne Marie Henriette Dior Ndione Nicholas Di Paola Gamou Fall André Pouwedeou Bedekelabou

Usutu virus (USUV) is a Culex-associated mosquito-borne flavivirus of the Flaviviridae family. Since its discovery in 1959, the virus has been isolated from birds, arthropods and humans in Europe and Africa. An increasing number of Usutu virus infections in humans with neurological presentations have been reported. Recently, the virus has been detected in bats and horses, which deviates from the currently proposed enzootic cycle of USUV involving several different avian and mosquito species. Despite this increasing number of viral detections in different mammalian hosts, the existence of a non-avian reservoir remains unresolved. In Kedougou, a tropical region in the southeast corner of Senegal, Usutu virus was detected, isolated and sequenced from five asymptomatic small mammals: Two different rodent species and a single species of shrew. Additional molecular characterization and in vivo growth dynamics showed that these rodents/shrew-derived viruses are closely related to the reference strain (accession number: AF013412) and are as pathogenic as other characterized strains associated with neurological invasions in human. This is the first evidence of Usutu virus isolation from rodents or shrews. Our findings emphasize the need to consider a closer monitoring of terrestrial small mammals in future active surveillance, public health, and epidemiological efforts in response to USUV in both Africa and Europe.

Enzootic

Flavivirus

Shrew

10.3390/v11020181

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Citations (58)