ABSTRACT
Human respiratory syncytial virus (RSV) infection remains as a major cause of morbidity and mortality among pediatric population. Immune response is poor and unable to establish a long term effective protection against this virus. Of particular interest has been the description of extrapulmonary manifestations of RSV infection in liver, kidney, endocrine system, heart and brain, associated to infection of peripheral blood. In the central nervous system (CNS), recent studies in animals have suggested long term neurocognitive impairment due to a direct damage from the virus. This was prevented in rats by a recombinant BCG vaccine expressing a nucleoprotein N of RSV that produces an effective immune response against the virus, not allowing its dissemination to the CNS. These findings in animal models highlight the importance of conducting more specific studies in children affected with severe infection by RSV. Therefore, our group is currently conducting an assessment of the possible long-term cognitive impairment in children under 2 years. The results of this study could be a strong argument to continue looking for an effective method for protecting against RSV infection.
La infección por virus respiratorio sincicial humano (VRS) es una de las principales causas de morbimortalidad en población pediátrica. La respuesta inmune generada contra VRS es poco eficiente para su eliminación y logra establecer sólo protección parcial contra infecciones posteriores. De especial interés en los últimos años ha sido la descripción de manifestaciones extra-pulmonares de la infección por VRS en hígado, riñón, sistema endocrino, corazón y cerebro. A nivel de sistema nervioso central (SNC), estudios recientes en modelos animales han sugerido problemas neurocognitivos a largo plazo derivados de un daño directo del virus en el cerebro. Este daño logró ser prevenido con vacuna experimental BCG recombinante, que expresa la nucleoproteína N de VRS e induce inmunidad efectiva, impidiendo la diseminación del virus hacia el SNC. Estos hallazgos en modelo animal han dado cuenta de la importancia de efectuar estudios más detallados en niños afectados por VRS grave. Por tal motivo, actualmente se está realizando una evaluación de la posible alteración cognitiva a largo plazo en niños bajo dos años de edad por parte de nuestro grupo. Los resultados de este estudio podrían significar un argumento muy importante para continuar en la búsqueda de un método efectivo de protección contra esta infección.
Subject(s)
Humans , Animals , Rats , Respiratory Syncytial Virus Infections/complications , Central Nervous System Viral Diseases/virology , Severity of Illness Index , Acute Disease , Disease Models, AnimalABSTRACT
Para estudar a epidemiologia e evolução do novo genótipo HRSVB denominado BA, caracterizado pela duplicação de 60 nt na proteína G, analisamos 4274 amostras clínicas coletadas de crianças hospitalizadas no Hospital Universitário/USP e Hospital da Santa Casa de Misericórdia, cidade de São Paulo entre os anos de 2001 e 2009. As amostras foram submetidas a RT-PCR seguido do sequenciamento da região G2 do gene G. A duplicação de 60 nt foi detectada em 104 (28.3%) das 367 amostras analisadas. De 2001 a 2004 a circulação do genótipo BA foi baixa, seguido de 85.4% (2005), 57.6% (2006), sem circulação (2007), 10% (2008) e 75% (2009) do total de amostras sequenciadas. As sequências foram comparadas com outras BA de diversos países do mundo. A análise filogenética preliminar dividiu as amostras brasileiras em 5 grupos (BA-I, BAII, BAIII, BAIV e BAVI), sendo que a maioria das amostras de 2005 a 2009 agruparam juntas na linhagem BA-IV, estabelecendo um grupo temporal e geográfico.
In order to study the epidemiology and evolution of the new genotype of HRSVB named BA characterized with a 60-nt duplication in the G protein we analyzed 4274 clinical samples collected from children hospitalized in University Hospital/USP and Santa Casa de Misericórdia Hospital, in São Paulo city, during 2001 to 2009. The samples were subject to RT-PCR followed by sequencing of the G2 region of the G gene. The 60 nt-duplication were detected in 104 (28.3%) of 367 sequencing samples. From 2001 to 2004 the circulation of the BA genotype was low, followed by 85.4% (2005), 57.6% (2006), no circulation (2007), 10% (2008) and 75% (2009) of total sequencing samples. Sequences were compared with G sequences with the 60 nt-duplication globally sampled. Preliminary phylogenetic analysis divided Brazilian samples into five clusters (BA-I, BAII, BAIII and BAVI and BAIV), and almost all samples from 2005 to 2009 were clustered together in BA-IV lineage, establishing temporal and geographical cluster.
Subject(s)
Humans , Child , Genotype , Noxae , Respiratory Syncytial Viruses/genetics , Respiratory Syncytial Virus, HumanABSTRACT
O Vírus respiratório sincicial humano (hRSV - human respiratory syncytial virus) e o Metapneumovírus humano (hMPV - human metapneumovirus) são os principais agentes etiológicos identificados nas infecções respiratórias agudas (IRAs). As IRAs representam importante causa de morbidade e mortalidade em crianças no mundo todo. hRSV e hMPV são membros da família Paramyxoviridae. São vírus envelopados, não-segmentados dotados de genoma de RNA de fita simples com sentido negativo. O hRSV é o agente viral melhor caracterizado neste grupo, associado à doença do trato respiratório inferior. Recentemente foi identificado um novo patógeno humano pertencente à subfamília Pneumovirinae, o hMPV, o qual possui similaridades com o hRSV, na sua organização genômica, estrutura viral, antigenicidade e sintomas clínicos. A subfamília Pneumovirinae contém dois gêneros: gênero Pneumovirus que contêm o hRSV, o RSV bovino (bRSV - bovine RSV), bem como os RSV ovino, caprino e o vírus da pneumonia murina, o segundo gênero Metapneumovirus que consiste do MPV aviário (aMPV - avian MPV) e hMPV. Neste trabalho, apresentamos uma breve revisão narrativa da literatura sobre aspectos importantes da biologia, epidemiologia e manifestações clínicas das infecções por estes dois vírus respiratórios.
The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are the main etiological agents of acute respiratory infections (ARIs). ARIs are an important cause of childhood morbidity and mortality worldwide. The hRSV and hMPV are members of the Paramyxoviridae family. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. The respiratory syncytial virus (hRSV) is the best characterized viral agent of this group, associated with respiratory diseases in the lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV), which is structurally similar to the hRSV in terms of genomic organization, viral structure, antigenicity, and clinical symptoms. The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains the hRSV, the bovine RSV (bRSV), as well as the ovine and caprine RSV and pneumonia virus of mice, the second genus Metapneumovirus, consists of the avian MPV (aMPV) and hMPV. In this study, we present a brief review of the literature on important aspects of the biology, epidemiology, and clinical manifestations of infections by two respiratory viruses.