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Sacramento, PR. Genetic diversity of Neuraminidase of Influenza A virus, isolated from children hospitalized in São Paulo city, from 1995 to 2006. [Master thesis]. São Paulo: Instituto de Ciências Biomédicas da Universidade de São Paulo; 2010. Influenza is one of the most important respiratory tract infections in humans, annually accounting for 3 to 5 million cases and nearly 250,000 to 500,000 deaths around the world. A striking feature of this virus is its extensive genetic and antigenic variability, especially in their surface proteins, neuraminidase (NA) and hemagglutinin (HA). This variability can happen either by point mutations that occur during replication (called drifts), as well as rearrangements of RNA segments of viruses that affect different species (shifts), generating a new virus to which the population has no immunity. Because of the serious medical and social problems, great efforts are made in the monitoring of circulating strains, both for the production of effective vaccine, and to quickly identify an emerging strain. The aim of this study was to characterize Influenza virus circulating in São Paulo city and the neuraminidase (NA) gene sequence of Influenzavirus A (IA) in samples from children hospitalized at Pediatric Infirmary, Nursery, and the Pediatric and Neo-natal Intensive Care Unit of the University Hospital of São Paulo, from 1995 to 2006. Clinical specimens from 3009 children aged <5 years, hospitalized with respiratory symptoms, underwent duplex RT-PCR for detection and typing of Influenza virus, followed by multiplex RT-PCR for subtyping of Influenza virus A. The NA gene of the positive samples for Influenza A virus was amplified and sequenced. Among the 3009 samples, 4.4% (n = 133) were positive for influenza virus, 88.0% (n = 116) for Influenza A and 12.0% (n = 16) for Influenza B. Among the samples of Influenza A, 94 were characterized as H3N2, 7 H1N1 and 16 were not subtyped by Multiplex RT-PCR. A total of 74 samples (71 H3N2 and 3 H1N1) had the NA gene sequenced (total or partially). The nucleotide sequences obtained were compared with nucleotide sequences of strains isolated in several regions of the world, and with sequences of vaccine strains recommended for the period. Brazilian samples were grouped in clusters with samples isolated in the same year, indicating much more a temporal variation than geographical, since the strains from different locations were in the same cluster. It was also found a good similarity between the circulating strains and vaccine strains recommended for the corresponding period, and no mutations were found related to the emergence of antiviral resistance to neuraminidase inhibitors.

Diversidade genética da neuraminidase de vírus Influenza A, isolados de crianças internadas na cidade de São Paulo, de 1995 a 2006.