Genetic stability and linkage analysis of the 2009 Influenza A(H1N1) virus based on sequence homology.
ABSTRACT The 2009 swine-origin Influenza A virus subtype H1N1 (S-OIV) is generally believed to be a mixture of human, bird and swine viruses, resulting from multiple reassortments. The evolutionary origin of the S-OIV is of high interest but still remains obscure. In order to understand the evolution of the new virus, we performed sequence homology, segment stability and segment linkage analysis, as well as analysis of the host and geographic distribution of the evolutionarily related viruses. Stability analysis demonstrated that segment 6 (NA) was the most unstable one, followed by segment 4 (HA), while the other 6 segments were relatively stable. Host and geographic distribution analysis indicated that all 8 segments of the new virus were closely related to those of swine influenza viruses circulating either in North America or in Eurasia. Segment linkage analysis showed that segments 1 (PB2), 2 (PB1), 3 (PA), 4 (HA), 5 (NP), and 8 (NS) are in linkage disequilibrium exclusively with North American swine influenza viruses, and segments 6 (NA) and 7 (M) are evolutionarily linked solely with Eurasian swine influenza viruses. Two North American swine strains and 2 Eurasian swine strains were identified as possible ancestors of S-OIV 2009. Based on the most recent linkage analysis with the updated influenza sequences, South Dakota avian strains were found to be the closest known relatives of S-OIV 2009.
- Oral Oncology - ORAL ONCOL. 01/2011; 47.
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ABSTRACT: Vaccines against emerging pathogens such as the 2009 H1N1 pandemic virus can benefit from current technologies such as rapid genomic sequencing to construct the most biologically relevant vaccine. A novel platform (Ad5 [E1-, E2b-]) has been utilized to induce immune responses to various antigenic targets. We employed this vector platform to express hemagglutinin (HA) and neuraminidase (NA) genes from 2009 H1N1 pandemic viruses. Inserts were consensuses sequences designed from viral isolate sequences and the vaccine was rapidly constructed and produced. Vaccination induced H1N1 immune responses in mice, which afforded protection from lethal virus challenge. In ferrets, vaccination protected from disease development and significantly reduced viral titers in nasal washes. H1N1 cell mediated immunity as well as antibody induction correlated with the prevention of disease symptoms and reduction of virus replication. The Ad5 [E1-, E2b-] should be evaluated for the rapid development of effective vaccines against infectious diseases.Vaccine 08/2011; 29(40):7020-6. · 3.77 Impact Factor
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ABSTRACT: Given the interconnected nature of our world today, emerging pathogens and pandemic outbreaks are an ever-growing threat to the health and economic stability of the global community. This is evident by the recent 2009 Influenza A (H1N1) pandemic, the SARS outbreak, as well as the ever-present threat of global bioterrorism. Fortunately, the biomedical community has been able to rapidly generate sequence data so these pathogens can be readily identified. To date, however, the utilization of this sequence data to rapidly produce relevant experimental results or actionable treatments is lagging in spite of obtained sequence data. Thus, a pathogenic threat that has emerged and/or developed into a pandemic can be rapidly identified; however, translating this identification into a targeted therapeutic or treatment that is rapidly available has not yet materialized. This commentary suggests that the growing technology of DNA synthesis should be fully implemented as a means to rapidly generate in vivo data and possibly actionable therapeutics soon after sequence data becomes available.Journal of pathogens. 01/2011; 2011:765763.