Interaction between a 1998 human influenza virus N2 neuraminidase and monoclonal antibody Mem5. (41/1009)

Influenza virus constantly escapes antibody inhibition by introducing mutations that disrupt protein-protein interactions. Based on the structure of the complex between neuraminidase (NA) of influenza A/Memphis/31/98 (H3N2) and the Fab of a monoclonal antibody (Mem5) that binds and inhibits the Memphis/98 NA, we investigated the contribution made by individual amino acids of NA to the stability of the complex. We made mutations D147A, D147N, H150A, H197A, D198A, D198N, E199A, E199Q, K221R, A246K, D251N, and D251A. Binding of each mutant to NA was quantitated by NA inhibition assays and ELISA. Most of the mutant NAs were inhibited by Mem5 to the same extent as wild-type, but with lower affinity. The exceptions were E199A, E199Q, and K221R, in which binding was abrogated. The ELISA results confirmed a correlation between NA inhibition and binding. The Mem5 epitope is dominated by a few high-energy interactions as was found in the epitope on an avian subtype N9 NA that binds antibody NC41 and different to the more diffuse energy distribution in the NC10 epitope on N9 NA. Energetic dominance of a particular interaction, which is associated with potential for antibody escape mutations, may be associated with the absence of water molecules in the vicinity. Critical contacts in a dominant antigenic site are likely to mutate, allowing some predictions of antigenic drift.  (+info)

Detailed analysis of the genetic evolution of influenza virus during the course of an epidemic. (42/1009)

The genetic variability of influenza virus is usually studied with sequences selected over numerous years and countries, and rarely within a single season. Here we examined the viral evolution and the correlation between genetic and clinical features during an epidemic. From a French prospective household-based study in 1999-2000, 99 infected patients were randomly selected. The HA1 genomic domain was sequenced. Phylogenetic analysis showed the existence of two groups of A/H3N2 viruses. We found no distinct pattern of genomic evolution within either group according to time. A spatial correlation with the nucleotide distances was shown. The average nucleotide diversity was 3.4x10-3 nucleotides per site, and did not differ between the groups. A lower number of segregating sites was observed in patients who experienced influenza-like symptoms during the previous epidemic. These results suggest that the influenza virus undergoes regular HA1 nucleotide changes, but without clonal expansion of mutant strains within a single epidemic.  (+info)

Quail carry sialic acid receptors compatible with binding of avian and human influenza viruses. (43/1009)

There is growing evidence that some terrestrial avian species may play a role in the genesis of influenza viruses with pandemic potential. In the present investigation, we examined whether quail, a widespread-farmed poultry, possess the proper characteristics for serving as an intermediate host for the zoonotic transmission of influenza viruses. Using a lectin-based staining based on specific agglutinins, we found that, in addition to the presence of sialic acid alpha2,3-galactose (SAalpha2,3-gal) linked receptors, there are abundant sialic acid alpha2,6-galactose (SAalpha2,6-gal) linked receptors in quail trachea and intestine. The presence of abundant SAalpha2,6-gal-linked receptors explains, at least in part, the circulation of avian influenza viruses with human-like receptor specificity in quail. In quail trachea, SAalpha2,3-gal linked receptors are present primarily in non-ciliated cells, while SAalpha2,6-gal linked receptors are localized predominantly on the surface of ciliated cells. In quail intestine, both types of receptors were found on epithelial cells as well as in crypts. In a solid-phase overlay binding assay, both avian and human influenza viruses bind to plasma membranes prepared from epithelial cells of quail trachea and intestine, strongly suggesting that these receptors are functional for binding of influenza viruses from different species. Together with previous observations, these results are consistent with the notion that quail could provide an environment for the spread of reassortants between avian and human influenza viruses, thus acting as a potential intermediate host.  (+info)

Molecular evolution of human influenza A/H3N2 virus in Asia and Europe from 2001 to 2003. (44/1009)

Hemagglutinin sequences of 146 human influenza A/H3N2 strains identified in respiratory specimens from Asia and Europe during the 2001-2003 influenza seasons were analyzed by DNA sequencing. Our results suggest that four amino acid substitutions, L25I, H75Q, H155T, and Q156H, led to the antigenic conversion of the previously predominant A/Panama/2007/99-like strains to the more recent A/Fujian/411/2002-like strains.  (+info)

Comparison of the Binax NOW Flu A enzyme immunochromatographic assay and R-Mix shell vial culture for the 2003-2004 influenza season. (45/1009)

The Binax NOW Flu A enzyme immunochromatographic assay was compared to viral culture with R-Mix shell vials for 455 nasal-wash or nasal-aspirate specimens. The overall sensitivity, specificity, positive predictive value, and negative predictive value of the assay were 64.9%, 98.4%, 89.3%, and 93.2%, respectively. However, the assay sensitivity decreased significantly with increasing patient age.  (+info)

Influenza-associated deaths among children in the United States, 2003-2004. (46/1009)

BACKGROUND: Although influenza is common among children, pediatric mortality related to laboratory-confirmed influenza has not been assessed nationally. METHODS: During the 2003-2004 influenza season, we requested that state health departments report any death associated with laboratory-confirmed influenza in a U.S. resident younger than 18 years of age. Case reports, medical records, and autopsy reports were reviewed, and available influenza-virus isolates were analyzed at the Centers for Disease Control and Prevention. RESULTS: One hundred fifty-three influenza-associated deaths among children were reported by 40 state health departments. The median age of the children was three years, and 96 of them (63 percent) were younger than five years old. Forty-seven of the children (31 percent) died outside a hospital setting, and 45 (29 percent) died within three days after the onset of illness. Bacterial coinfections were identified in 24 of the 102 children tested (24 percent). Thirty-three percent of the children had an underlying condition recognized to increase the risk of influenza-related complications, and 20 percent had other chronic conditions; 47 percent had previously been healthy. Chronic neurologic or neuromuscular conditions were present in one third. The mortality rate was highest among children younger than six months of age (0.88 per 100,000 children; 95 percent confidence interval, 0.52 to 1.39 per 100,000). CONCLUSIONS: A substantial number of influenza-associated deaths occurred among U.S. children during the 2003-2004 influenza season. High priority should be given to improvements in influenza-vaccine coverage and improvements in the diagnosis and treatment of influenza to reduce childhood mortality from influenza.  (+info)

Influenza and respiratory syncytial virus morbidity among 0-19 aged group in Yunus Emre Health Center. (47/1009)

The objective of the study was to determine the morbidity of influenza and respiratory syncytial virus (RSV) infection in the 0-19 years of age group with influenza-like illness among the outpatient cases. From 20 January to 31 March 2003 a total of 123 subjects with upper respiratory tract infection attended Yunus Emre Health Center. Ninety-one subjects fit the case definition of influenza-like illness, which consisted of acute fever of more than 38 degrees C, cough, and sore throat. After obtaining their consent, nasal swabs were taken for isolation of influenza and RSV. Of these, 10 were influenza A virus, 6 were influenza B virus and 20 were RSV. All of influenza virus A was typed as subtype H3N2. The rates of influenza virus among 5-9 and 1-4 years of age groups and of RSV among 1-4 years of age group were high. The average number of absentee days of schoolchildren with influenza was 3.33 days and of those with RSV infection was 1.43 days; this rate was calculated as 2.25 days for the influenza-like illness. Continuous surveillance and influenza vaccination for target groups are recommended for beneficial effects of reducing influenza morbidity and mortality in the community.  (+info)

Variation in the ability of human influenza A viruses to induce and inhibit the IFN-beta pathway. (48/1009)

We investigated the ability of a selection of human influenza A viruses, including recent clinical isolates, to induce IFN-beta production in cultured cell lines. In contrast to the well-characterized laboratory strain A/PR/8/34, several, but not all, recent isolates of H3N2 viruses resulted in moderate IFN-beta stimulation. Through the generation of recombinant viruses, we were able to show that this is not due to a loss of the ability of the NS1 genes to suppress IFN-beta induction; indeed, the NS1 genes behaved similarly with respect to their abilities to block dsRNA signaling. Interestingly, replication of A/Sydney/5/97 virus was less susceptible to pre-treatment with IFN-alpha than the other viruses. In contrast to the universal effect on dsRNA signaling, we noted differences in the effect of NS1 proteins on expression of interferon stimulated genes and also genes induced by a distinct pathway. The majority of NS1 proteins blocked expression from both IFN-dependent and TNF-dependent promoters by an apparent post-transcriptional mechanism. The NS1 gene of A/PR/8/34 NS1 did not confer these blocks. We noted striking differences in the cellular localization of different influenza A virus NS1 proteins during infection, which might explain differences in biological activity.  (+info)