Disease relevance of Influenza A Virus, H1N1 Subtype

• We assessed the contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68 (H3N2) virus [1].
• In one patient, dissemination of type A (H1N1) virus to the myocardium was demonstrated, and viremia complicated the clinical course despite the use of oral amantadine HCl and ribavirin aerosol [2].
• These viruses contain HA, NA and M genes derived from influenza A/WSN/33 H1N1 virus (mouse-adapted), and the remaining five genes from human influenza A/Victoria/3/75 virus [3].
• Intranasal live attenuated cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant virus and parenteral inactivated influenza A/Taiwan/1/86 (H1N1) virus were given alone or in combination to 80 ambulatory elderly subjects [4].
• Antibody responses and protection against influenza virus infection in different congenic strains of mice immunized intranasally with adjuvant-combined A/Beijing/262/95 (H1N1) virus hemagglutinin or neuraminidase [5].

High impact information on Influenza A Virus, H1N1 Subtype

• FINDINGS: The H5N1/97 viruses induced much higher gene transcription of proinflammatory cytokines than did H3N2 or H1N1 viruses, particularly TNF alpha and interferon beta [6].
• With H1N1 viruses, an arrest of significant evolution of the NA discordant with the continuing antigenic drift of HA was found in the 1980-1983 period [7].
• It appears that only the HA, NA, M, and NS genes of this virus are derived from the earlier H1N1 viruses and that the P1, P2, P3, and NP genes most likely originate from an H3N2 parent [8].
• However, we demonstrated that unlike H1N1 virus, H5N1/97 strongly activates mitogen-activated protein kinase (MAPK), including p38 MAPK and extracellular signal-regulated kinases 1 and 2 [9].
• Generation and characterization of recombinant influenza A (H1N1) viruses harboring amantadine resistance mutations [10].

Chemical compound and disease context of Influenza A Virus, H1N1 Subtype

• Volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) virus and treated with the neuraminidase (NA) inhibitor oseltamivir were monitored for the emergence of drug-resistant variants [11].
• Susceptible volunteers were randomized to receive either saline or zanamivir (600 mg) intravenously twice daily for 5 days beginning 4 h prior to intranasal inoculation with approximately 10(5) 50% tissue culture infectious doses (TCID50) of influenza A/Texas/36/91 (H1N1) virus [12].
• Treatment of influenza A (H1N1) virus infection with ribavirin aerosol [13].
• Subjects were cloistered for 8 days and challenged with a rimantadine-sensitive strain of influenza A H1N1 virus at the end of the first day [14].
• The efficacy and safety of oral LY217896 for prevention of experimental influenza A/Kawasaki/86 (H1N1) virus infection were assessed in susceptible males randomly assigned to receive LY217896 (75 mg) or placebo once daily for 7 days beginning 24 h prior to viral challenge [15].

Biological context of Influenza A Virus, H1N1 Subtype

• In this study, reverse genetics was used to generate and characterize recombinant influenza A (H1N1) viruses harboring L26F, V27A, A30T, S31N, G34E, and V27A/S31N mutations in the M2 gene [10].
• Thirty-one strains of human influenza A (H1N1) viruses isolated in Europe, mostly in Finland, from 1978-1992 were compared with respect to their nucleotide sequences coding for the HA1 portion of haemagglutinin [16].
• Immune response of human volunteers and animals to vaccination with egg-grown influenza A (H1N1) virus is influenced by three amino acid substitutions in the haemagglutinin molecule [17].
• In addition, both of the plasmid DNA mixtures (HA + NA) and (HA + NA + M1) showed a slight tendency to provide cross-protection against an A/Yamagata/120/86 (H1N1) virus challenge, and this was accompanied by a relatively high level of cross-reacting antibodies [18].
• The combination in recombinant X/28 (H1N1) of haemagglutinin and neuraminidase of A/Brazil/11/78 (H1N1) virus and othercomponents of A/Leningrad/9/46 virus determines its high affinity to the epithelium of the upper respiratory tract of humans, as well as its marked virulence for seronegative volunteers [19].

Anatomical context of Influenza A Virus, H1N1 Subtype

• RESULTS: We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro [20].

Gene context of Influenza A Virus, H1N1 Subtype

• Samples taken at the time of admission proved to be strongly positive for Adenovirus by PCR, but negative for Influenza A/H1N1 virus, Influenza A/H3N2 virus, Influenza B virus, Respiratory syncytial virus, and SARS coronavirus [21].
• The oligonucleotide pattern of A/California/45/78 viral RNA was markedly different from that of other 1977-1978 H1N1 viruses; the major change occurred in the polymerase and nucleoprotein genes [22].
• Reassortment experiments between a group 1 virus (A/Aichi/4/92) or a group 2 virus (A/Aichi/24/92) and the A/WSN/33 influenza A (H1N1) virus strain suggested that the HA gene products of the viruses of both groups had lost the capacity to agglutinate CRBC [23].
• The involvement of the B type virus-specific immunity in this protection was suggested by the absence of protection against B/Ibaraki virus infection in mice previously inoculated with both A/PR/8/34 (H1N1) virus HA vaccine and CTB [24].
• INTERVENTIONS: Mice were inoculated intranasally with H1N1 virus [25].

Analytical, diagnostic and therapeutic context of Influenza A Virus, H1N1 Subtype

• In a neuraminidase (NA) gene rescue system, we were able to demonstrate that electroporation of in vitro reconstituted NA RNP of influenza A/WSN/33 (H1N1) virus into WSN/HK virus infected cells allows the rescue of the transfectant WSN virus [26].

References