Toll-like receptor 3 (TLR3) and the development of type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is a chronic, progressive autoimmune disease characterized by metabolic decompensation often leading to dehydration and ketoacidosis. Viral agents seem to play an important role in triggering the autoimmune destruction that leads to the development of T1DM. Among several viral strains investigated so far, the enterovirus family has been consistently associated with the onset of T1DM in humans. One of the mediators of viral damage is the double-stranded RNA (dsRNA) generated during replication and transcription of viral RNA and DNA. The Toll-like receptor 3 (TLR3) gene codes for an endoplasmic receptor of the pattern-recognition receptors (PRRs) family that recognizes dsRNA, plays an important role in the innate immune response triggered by viral infection. Binding of dsRNA to the TLR3 triggers the release of proinflammatory cytokines, such as interferons, which exhibit potent antiviral action; thus, protecting uninfected cells and inducing apoptosis of infected ones. Therefore, the TLR3 gene is a good candidate for the development of T1DM. Within this context, the objective of the present review was to address the role of the TLR3 gene in the development of T1DM. Arch Endocrinol Metab. 2015;59(1):4-12.

Molecular and seroepidemiologic studies of Enterovirus 71 infection in the State of Pará, Brazil

Em muitos países, o Enterovírus 71 (EV-71) família Picornaviridae é associado a doença de pé-mão e boca e doenças neurológicas agudas enquanto que no Brasil esse vírus está mais associado às últimas. O objetivo desta pesquisa foi utilizar em estudos moleculares e soroepidemiológicos, o primeiro isolamento de EV-71 obtido na região norte do Brasil. No período de janeiro de 1998 a dezembro de 2000 foram coletadas 88 amostras (44 casos de PFA) de fezes das quais, duas (2,2%) foram positivas para EV-71 (73442/PA/99). A seqüência de nucleotídeos do gen que codifica a proteína VP1 mostrou que o isolado 73442/PA/99 foi similar às cepas de EV-71 pertencentes ao grupo B- mais próxima das norte americanas. Teste de neutralização com 389 amostras de soro colhidas no período de janeiro de 1998 a novembro de 2001, de indivíduos com idade de 0 a 15 anos residentes na cidade de Belém, Estado do Pará mostrou os seguintes resultados em relação ao isolado 73442/PA/99 e ao protótipo BrCr: 207 indivíduos (53,2%) tinham anticorpos neutralizantes para ambos os vírus, 167 (42,9%) não tinham anticorpos e 15 tinham anticorpos para um dos dois vírus. Somente 20,2% das crianças com idade de 0 a 3 anos tinham anticorpos neutralizantes para EV-71, indicando que essas crianças estavam mais suscetíveis à infecção. Tanto o estudo de soroprevalência quanto o de sequenciamento da VP1 foram importantes para demonstrar a propagação e o padrão molecular do EV-71 circulante na região norte do Brasil.

Cloning and expression of Protease 2 from Coxsakievirus B3

Protease 2A [2Apro] of coxsackievirus B3 [CVB3] plays a major role in viral replication. In case of infection, viral proteins are being synthesized from viral mRNA using host biosynthesis machinery. 2Apro of virus, after being synthesized, exhibits two critical functions, cleavage of viral proteins and breaking eukaryotic initiation factor 4G. The enzyme plays an essential role in viral replication and cellular damage. To understand pathogenicity of infection and also developing potent and selective inhibitors against picornavirus infection, it is necessary to prepare pure 2Apro enzyme. cDNA of 2Apro was synthesized using in vitro infection of permissive host through reverse transcription process and was cloned in pET22b[+]. Since 2Apro is a toxic product, its expression will act on host before induction and damages the cells. For this reason, different hosts were checked and finally BLR[DE3]pLysS, which carries an extra-plasmid for lysozyme expression, that minimizes unwanted target protein products [leakage] was selected. By employing such expression system we could minimize the unwanted expression of 2Apro. Though it is not possible to avoide it, but seems negligible. Hence, this system is useful for expression of toxic proteins in sensitive hosts in order to prevent bacterial damage. The product was confirmed by SDS polyacrylamide gel electrophoresis and immunoblot analysis

Mecanismo de participación de los Enterovirus en la neuropatía epidémica. Hipótesis fisiopatológica / Mechanism of participation of the enterovirus in the epidemic neuropathy. Physiopathological hypotheses

Durante la neuropatía epidémica ocurrida en Cuba en los años 1992 y 1993, se obtuvieron del líquido cefalorraquídeo de pacientes aislamientos virales relacionados antigénicamente con los virus Coxsackie. Conjuntamente con las investigaciones virológicas se efectuaron otras de tipo epidemiológicas, toxicológicas, nutricionales, inmunológicas e histopatológicas. A pesar que la enfermedad estuvo unida a factores tóxicos-nutricionales, no ha sido posible identificar la causa de la epidemia. Teniendo en consideración los resultados obtenidos en las distintas investigaciones, hemos formulado una hipótesis integral, multifactorial, para explicar el mecanismo fisiopatológico de la participación de los virus aislados como mediadores de un proceso de autoinmunidad en la patogenia de la enfermedad

An epidemic of viral acute haemorrhagic conjunctivitis in Delhi in 1994.

An epidemic of acute haemorrhagic conjunctivitis affecting persons of all ages and both sexes occurred in Delhi and surrounding areas during the monsoon season of 1994. The symptoms lasted on an average for 4-5 days. In some of the patients corneal involvement was observed. Conjunctival swabs from the affected patients were processed for viral antigen detection, virus isolation and bacterial culture and sensitivity. Viral antigen was detected in 62% (31/50) of the smears tested by indirect immunofluorescence assay. In 22 (44%) of the specimens Coxackie A 24 (Cox A 24) virus antigen and in 9 (18%) of the specimens Entero Virus 70 (EV 70) antigen were detected. In confluent monolayers of Hep 2 cells cytopathic virus was isolated in 10 (30.30%) of the 33 specimens processed. The isolated viruses were identified as either Cox A 24 (7 isolates) or EV 70 (3 isolates) using indirect immunofluorescence assay. Super added bacterial infection was observed in 33% (89/270) of the cases, Staphylococcus albus being the predominant bacteria isolated.

Enterovírus-70 na regiäo metropolitana de Säo Paulo, Brasil, de l984 a1987: aspectos da infecçäo em períodos epidêmicos e endêmico / Enterovirus 70 in the metropolitan region of Säo Paulo, Brazil, from 1984 to 1987: infection aspects in endemic and epidemic periods

Säo apresentados os resultados dos estudos sobre o comportamento do Enterovirus-70 (EV-70) na regiäo metropolitana de Säo Paulo desde sua provável introduçäo no veräo de 1984, determinando extensa de conjuntivite hemorrágica aguda (C.H.A.), até o final de 1987 abrangendo preríodo em que este agravo foi pouco notado. Na fase epidêmica ocorrida no primeiro trimestre de 1984 foram estudados 291 indivíduos divididos em três grupos denominados A, B e C, o primeiro formado por pessoas atingidas pela C.H.A. e os outros dois por indivíduos näo atingidos por este agravo mas que, respectivamente, referiam contato domiciliar com casos de C.H.A. e os que näo referiam o citado contato. A demonstraçäo de anticorpos se fez pela técnica de imunofluorescência (IFI) para detectar IgM específico para EV-70 e pela prova de neutralizaçäo em cultura de células BHK-21. Verificou-se que 56,7%,33,3%e 20,6% dos indivíduos pertencentes, respectivamente, aos grupos A,B e C apresentavam anticorpos específicos da classe IgM. No grupo A a faixa etária mais atingida foi a de 10 a 29 anos. No período que vai do fim da primeira e única epidemia até o final de 1987, identificaram-se três casos esporádicos de C.H.A. e 10 pacientes com afecçäo neurológica aguda associada à infecçäo recente pelo EV-70. Nove, destes 10 casos, apresentaram paralisia de nervos cranianos, todos evoluindo sem sequelas clinicamente discerníveis. As formas assintomáticas e os casos esporádicos de C.H.A. e de afecçoes neurológicas mantiveram a circulaçäo do EV-70 no período epidêmico

Conjuntivite hemorrágica aguda causada pela variante do coxsackievirus A24, em Belém, Pará, Brasil, 1987 / Acute hemorrhagic conjunctivitis caused by a variant of coxsackievirus A24, in Belém, Pará, Brazil, 1987

Durante um surto de conjuntivite hemorrágica aguda (CHA), ocorrido em Belém, Pará, Brasil, em 1987, foi feita investigaçäo etiológica clínica e laboratorial, atendidos 83 pacientes e colhidos espécimes da conjuntiva, orofaringe e soro. Na linhagem celular HEP-2 obteve-se 73 isolamentos de um enterovirus posteriormente identificado pelo Centers for Disease Control (CDC), Atlanta, Georgia, USA, como sendo uma variante do coxsackievirus A24. Em 56 pares de soro foram realizados testes de neutralizaçäo para o EV70 e para a cepa isolada, tendo havido 57%(32) de conversäo sorológica para essa última

An outbreak of acute conjunctivitis caused by coxsackievirus A24 in Kuala-Lumpur, Malaysia, 1978.

An investigation of an outbreak of acute conjunctivitis in Kuala Lumpur from May to August 1978 was made. A total of 2,133 cases was involved, most of whom were adult Malay males of low income status from the surrounding villages and low-cost flats. The majority of cases had bilateral conjunctivitis with clear discharge. Pain and subconjunctival haemorrhage were not common and recovery, mostly without complications, occurred within 1 week. Eye scrapings and paired sera specimens were examined and the causal agent was found to be Coxsackievirus A24 (CA24).

Acute haemorrhagic conjunctivitis in Hong Kong 1971-1975.

Acute haemorrhagic conjunctivitis occurred in epidemic in Hong Kong in 1971 and 1975 respectively. Two picornaviruses, the Enterovirus type 70 and an antigenic variant of Coxsackie virus type A24, were isolated during the 1971 outbreak, while only the latter virus was detected in the 1975 outbreak. In 1972 and 1974, sporadic cases of conjunctivitis associated with Enterovirus type 70 were observed. Serological survey in late 1975 showed a high proportion of the population might still be susceptible to both viruses. Recrudescence of the disease is conceivable when environmental condition is favourable for the spread of these viruses.