Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil

Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses

Re?emergence of a coxsackievirus A24 variant causing acutehemorrhagic conjunctivitis in Brazil from 2017 to 2018

AbstractA large outbreak (over 200,000 cases) of acute hemorrhagic conjunctivitis (AHC) took place in Brazil during the summerof 2017/2018, seven years after a nationwide epidemic, which occurred in 2011. To identify the etiological agent, 80conjunctival swabs from patients with a clinical presentation suggestive of AHC were analyzed at the national enteroviruslaboratory. Real-time RT-PCR for human enteroviruses was performed, and enterovirus RNA was detected in 91.25% (73/80)of the specimens. Twenty-nine swab fluids were used to inoculate cell cultures (RD and Hep2C), and 72.4% (21/29) yieldeda cytopathic effect. Genotype IV coxsackievirus A24v (CV-A24v) was identified as the causative agent of the outbreak.Phylogenetic analysis based on the VP1 gene revealed that Brazilian isolates were genetically related to strains that causedan outbreak in French Guiana in 2017. Our results show the re-emergence of CV-A24v causing AHC outbreaks in Brazilbetween the end of 2017 and the beginning of 2018

Current Understanding of the Role of Cholesterol in the Life Cycle of Alphaviruses

Enveloped viruses rely on different lipid classes present in cell membranes to accomplish several steps of their life cycle in the host. Particularly for alphaviruses, a medically important group of arboviruses, which are part of the Togaviridae family, cholesterol seems to be a critical lipid exploited during infection, although its relevance may vary depending on which stage of the virus life cycle is under consideration and whether infection takes place in vertebrate or invertebrate hosts. In this review, the role of cholesterol in both early and late events of alphavirus infection and how viral replication may affect cholesterol metabolism are summarized, taking into account studies on Old World and New World alphaviruses in different cell lines. Moreover, the importance of cholesterol for the structural stability of alphavirus particles is also discussed, shedding light on the role played by this lipid when they leave the host cell

Current understanding of the role of cholesterol in the life cycle of Alphaviruses

This work was supported by the Brazilian research funding agencies Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes).Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil.Universidade do Estado do Pará. Departamento de Patologia. Centro de Ciências Biológicas e da Saúde. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Instituto Euro-Americano de Educação. Centro Universitário Metropolitano da Amazônia, Ciência e Tecnologia. Belém, PA, Brazil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Centro Nacional de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brazil.Enveloped viruses rely on different lipid classes present in cell membranes to accomplish several steps of their life cycle in the host. Particularly for alphaviruses, a medically important group of arboviruses, which are part of the Togaviridae family, cholesterol seems to be a critical lipid exploited during infection, although its relevance may vary depending on which stage of the virus life cycle is under consideration and whether infection takes place in vertebrate or invertebrate hosts. In this review, the role of cholesterol in both early and late events of alphavirus infection and how viral replication may affect cholesterol metabolism are summarized, taking into account studies on Old World and New World alphaviruses in different cell lines. Moreover, the importance of cholesterol for the structural stability of alphavirus particles is also discussed, shedding light on the role played by this lipid when they leave the host cell

Enterovirus B74 associated with hand, foot and mouth disease

Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, BraziMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Enterovírus. Ananindeua, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, BraziEnterovirus 74 (EV-B74) has been associated with cases of acute flaccid paralysis (AFP) but it is not a commonly found enterovirus. In this work, we present the characterization of an EV-B74 detected from the serum sample of a one-year-old boy presenting with signs and symptoms clinically compatible with hand, foot and mouth disease (HFMD). This is the first report of EV-B74 in Brazil

Enteroviruses associated with hand, foot, and mouth disease in Brazil

Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil

Re-emergence of a coxsackievirus A24 variant causing acute hemorrhagic conjunctivitis in Brazil from 2017 to 2018

This work was funded by a grant from the SVS/CGLAB, Brazilian Ministry of Health.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Referência Regional em Enteroviroses. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Referência Regional em Enteroviroses. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Referência Regional em Enteroviroses. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Referência Regional em Enteroviroses. Ananindeua, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterovírus. Rio de Janeiro, RJ, Brazil.A large outbreak (over 200,000 cases) of acute hemorrhagic conjunctivitis (AHC) took place in Brazil during the summer of 2017/2018, seven years after a nationwide epidemic, which occurred in 2011. To identify the etiological agent, 80 conjunctival swabs from patients with a clinical presentation suggestive of AHC were analyzed at the national enterovirus laboratory. Real-time RT-PCR for human enteroviruses was performed, and enterovirus RNA was detected in 91.25% (73/80) of the specimens. Twenty-nine swab fluids were used to inoculate cell cultures (RD and Hep2C), and 72.4% (21/29) yielded a cytopathic effect. Genotype IV coxsackievirus A24v (CV-A24v) was identified as the causative agent of the outbreak. Phylogenetic analysis based on the VP1 gene revealed that Brazilian isolates were genetically related to strains that caused an outbreak in French Guiana in 2017. Our results show the re-emergence of CV-A24v causing AHC outbreaks in Brazil between the end of 2017 and the beginning of 2018

Fusion of a new world Alphavirus with membrane microdomains involving partially reversible conformational changes in the viral spike proteins

This work was supported by an international grant from International Centre for Genetic Engineering and Biotechnology (ICGEB) and by Brazilian grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Programa de Apoio ao Desenvolvimento Cientıfíco e Tecnológico (PADCT), and Programa de Apoio a Nucleos de Excelência (PRONEX).Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brazil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brazil / Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brazil.Alphaviruses are enveloped arboviruses mainly proposed to infect host cells by receptor-mediated endocytosis followed by fusion between the viral envelope and the endosomal membrane. The fusion reaction is triggered by low pH and requires the presence of both cholesterol and sphingolipids in the target membrane, suggesting the involvement of lipid rafts in the cell entry mechanism. In this study, we show for the first time the interaction of an enveloped virus with membrane microdomains isolated from living cells. Using Mayaro virus (MAYV), a New World alphavirus, we verified that virus fusion to these domains occurred to a significant extent upon acidification, although its kinetics was quite slow when compared to that of fusion with artificial liposomes demonstrated in a previous work. Surprisingly, when virus was previously exposed to acidic pH, a condition previously shown to inhibit alphavirus binding and fusion to target membranes as well as infectivity, and then reneutralized, its ability to fuse with membrane microdomains at low pH was retained. Interestingly, this observation correlated with a partial reversion of low pH-induced conformational changes in viral proteins and retention of virus infectivity upon reneutralization. Our results suggest that MAYV entry into host cells could alternatively involve internalization via lipid rafts and that the conformational changes triggered by low pH in the viral spike proteins during the entry process are partially reversible

Inhibition of Mayaro virus infection by bovine lactoferrin

Submitted by Repositório Arca ([email protected]) on 2019-03-07T16:42:54Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) F94-1-s2.0-S004268221400035X-main.pdf: 1939209 bytes, checksum: bfe711d42ac15f7170188f4c04fe2ef3 (MD5)Approved for entry into archive by monique santos ([email protected]) on 2019-03-12T17:55:27Z (GMT) No. of bitstreams: 2 F94-1-s2.0-S004268221400035X-main.pdf: 1939209 bytes, checksum: bfe711d42ac15f7170188f4c04fe2ef3 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-03-12T17:55:27Z (GMT). No. of bitstreams: 2 F94-1-s2.0-S004268221400035X-main.pdf: 1939209 bytes, checksum: bfe711d42ac15f7170188f4c04fe2ef3 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2014Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Bioquímica. Instituto Biomédico. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Mayaro virus (MAYV) is an arbovirus linked to several sporadic outbreaks of a highly debilitating febrile illness in many regions of South America. MAYV is on the verge of urbanization from the Amazon region and no effective antiviral intervention is available against human infections. Our aim was to investigate whether bovine lactoferrin (bLf), an iron-binding glycoprotein, could hinder MAYV infection. We show that bLf promotes a strong inhibition of virus infection with no cytotoxic effects. Monitoring the effect of bLf on different stages of infection, we observed that virus entry into the cell is the heavily compromised event. Moreover, we found that binding of bLf to the cell is highly dependent on the sulfation of glycosaminoglycans, suggesting that bLf impairs virus entry by blocking these molecules. Our findings highlight the antiviral potential of bLf and reveal an effective strategy against one of the major emerging human pathogens in the neotropics

Analysis of Coxsackievirus B5 Infections in the Central Nervous System in Brazil: Insights into Molecular Epidemiology and Genetic Diversity

Coxsackievirus B5 (CVB5) is one of the most prevalent enteroviruses types in humans and causes annual epidemics worldwide. In the present study, we explored viral genetic diversity, molecular and epidemiological aspects of CVB5 obtained from cerebrospinal fluid and stool samples of patients with aseptic meningitis or acute flaccid paralysis, information that is still scarce in Brazil. From 2005 to 2018, 57 isolates of CVB5 were identified in the scope of the Brazilian Poliomyelitis Surveillance Program. Phylogenetic analyses of VP1 sequences revealed the circulation of two CVB5 genogroups, with genogroup B circulating until 2017, further replaced by genogroup A. Network analysis based on deduced amino acid sequences showed important substitutions in residues known to play critical roles in viral host tropism, cell entry, and viral antigenicity. Amino acid substitutions were investigated by the Protein Variation Effect Analyzer (PROVEAN) tool, which revealed two deleterious substitutions: T130N and T130A. To the best of our knowledge, this is the first report to use in silico approaches to determine the putative impact of amino acid substitutions on the CVB5 capsid structure. This work provides valuable information on CVB5 diversity associated with central nervous system (CNS) infections, highlighting the importance of evaluating the biological impact of certain amino acids substitutions associated with epidemiological and structural analyses