Phone: (405) 271-2227
Phone: (405) 271-2085 ext. 48824
Fax: (405) 271-3205
940 S.L. Young Blvd., BMSB 840A
Oklahoma City, OK 73104
PhD, University of New South Wales (Australia), 1971
Molecular studies of influenza virus.
Influenza occurs every winter, usually peaking in January in the northern hemisphere. Approximately 20,000 deaths in the US per year are attributed to influenza, many among elderly patients who have medical conditions that increase the likelihood of complications from influenza. Influenza is a significant disease in all age groups; an acute febrile illness with myalgia, headache, fever and cough. A rule-of-thumb for deciding if you have influenza rather than another respiratory virus is that if you really can't get out of bed, it's probably flu. The acute stage lasts about 3 days, but cough and malaise may last for some weeks. Influenza viruses currently circulating in the human population are classified serologically as type A (H1N1, H3N2) and type B. "H" and "N" refer to the viral surface glycoproteins hemagglutinin (HA) and neuraminidase (NA), and subtypes (e.g. 1, 3) do not cross-react in antibody tests.
Influenza vaccines are safe although somewhat variable in effect, depending on the age and immunocompetence of the vaccinee as well as the similarity of each vaccine strain to the circulating viruses. Influenza viruses undergo progressive antigenic drift; an accumulation of mutations that alter antigenic properties. Occasionally there is an antigenic shift, introducing new antigens into human influenza viruses from bird or animal viruses. Vaccine manufacture is therefore complicated by the need to update the components every year in response to mutations that alter antigenic reactivity.
Our research has had two branches, one to find ways of designing better vaccines, and the second to investigate how the virus gains entry into cells and how infection might be blocked by antiviral drugs.
Recent research highlights:
Demonstration that increase in antibodies after vaccination is inversely proportional to pre-existing antibody levels (Feng et al., 2009)
Crystal structure of an antibody bound to NA shows that an N-linked glycan is part of the epitope (Venkatramani et al., 2006).
Human influenza viruses of the H3N2 subtype have changed binding specificity as antigenic drift mutations accumulate (Gulati et al., 2013).
The structure of a new NA inhibitor bound in the active site (Venkatramani et al., 2014)
Demonstration of immunodominance of certain antigenic sites that may allow prediction of antigenic drift (Popova et al., 2012)
- Alymova IV, York IA, Air GM, Cipollo JF, Gulati S, Baranovich T, Kumar A, Zeng H, Gansebom S, McCullers JA. 2016. Glycosylation changes in the globular head of H3N2 influenza hemagglutinin modulate receptor binding without affecting virus virulence. Sci Rep.6:36216. PubMed PMID: 27796371; PMCID: PMC5086918.
- Kocer ZA, Krauss S, Zanin M, Danner A, Gulati S, Jones JC, Friedman K, Graham A, Forrest H, Seiler J, Air GM, Webster RG. 2015. Possible basis for the emergence of H1N1 viruses with pandemic potential from avian hosts. Emerg Microbes Infect.4(7):e40. PubMed PMID: 26251829; PMCID: PMC4522614.
- Air GM. 2015. Influenza virus antigenicity and broadly neutralizing epitopes. Curr Opin Virol.11:113-21. PubMed PMID: 25846699; PMCID: 4456283.
- Jia N, Barclay WS, Roberts K, Yen HL, Chan RW, Lam AK, Air G, Peiris JS, Dell A, Nicholls JM, Haslam SM. 2014. Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies. J Biol Chem.289(41):28489-504. PubMed PMID: 25135641; PMCID: 4192499.
- Gulati S, Lasanajak Y, Smith DF, Cummings RD, Air GM. 2014. Glycan array analysis of influenza H1N1 binding and release. Cancer Biomark.14(1):43-53. Epub 2014/03/20. PubMed PMID: 24643041.
- Air GM. 2014. Influenza virus-glycan interactions. Curr Opin Virol.7:128-33. PubMed PMID: 25061947; PMCID: 4149921.
- Walther T, Karamanska R, Chan RW, Chan MC, Jia N, Air G, Hopton C, Wong MP, Dell A, Malik Peiris JS, Haslam SM, Nicholls JM. 2013. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS Pathog.9(3):e1003223. Epub 2013/03/22. PubMed PMID: 23516363; PMCID: 3597497.
- Tappert MM, Porterfield JZ, Mehta-D'Souza P, Gulati S, Air GM. 2013. Quantitative comparison of human parainfluenza virus hemagglutinin-neuraminidase receptor binding and receptor cleavage. J Virol.87(16):8962-70. Epub 2013/06/07. PubMed PMID: 23740997; PMCID: 3754076.
- Gulati S, Smith DF, Cummings RD, Couch RB, Griesemer SB, St George K, Webster RG, Air GM. 2013. Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread. PLoS One.8(6):e66325. Epub 2013/06/28. PubMed PMID: 23805213; PMCID: 3689742.
- Venkatramani L, Johnson ES, Kolavi G, Air GM, Brouillette WJ, Mooers BH. 2012. Crystal structure of a new benzoic acid inhibitor of influenza neuraminidase bound with a new tilt induced by overpacking subsite C6. BMC Struct Biol.12:7. Epub 2012/05/09. PubMed PMID: 22559154; PMCID: 3416664.
- Popova L, Smith K, West AH, Wilson PC, James JA, Thompson LF, Air GM. 2012. Immunodominance of Antigenic Site B over Site A of Hemagglutinin of Recent H3N2 Influenza Viruses. PLoS One.7(7):e41895. Epub 2012/08/01. PubMed PMID: 22848649; PMCID: 3405050.
Among the most cited over the years:
- Air GM, Thompson EO, Richardson BJ, Sharman GB. Amino-acid sequences of kangaroo myoglobin and haemoglobin and the date of marsupial-eutherian divergence. Nature. 1971;229(5284):391-4.
- Barrell BG, Air GM, Hutchison CA, 3rd. Overlapping genes in bacteriophage phiX174. Nature. 1976;264(5581):34-41.
- Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR, Fiddes CA, Hutchison CA, Slocombe PM, Smith M. Nucleotide sequence of bacteriophage phi X174 DNA. Nature. 1977;265(5596):687-95.
- Air GM. Nucleotide sequence coding for the "signal peptide" and N terminus of the hemagglutinin from an asian (H2N2) strain of influenza virus. Virology. 1979;97(2):468-72.
- Laver WG, Air GM, Webster RG, Gerhard W, Ward CW, Dopheide TA. Antigenic drift in type A influenza virus: sequence differences in the hemagglutinin of Hong Kong (H3N2) variants selected with monoclonal hybridoma antibodies. Virology. 1979;98(1):226-37.
- Air GM. Sequence relationships among the hemagglutinin genes of 12 subtypes of influenza A virus. Proc Natl Acad Sci U S A. 1981;78(12):7639-43. PMCID: 349324.
- Webster RG, Laver WG, Air GM, Schild GC. Molecular mechanisms of variation in influenza viruses. Nature. 1982;296(5853):115-21.
- Laver WG, Colman PM, Webster RG, Hinshaw VS, Air GM. Influenza virus neuraminidase with hemagglutinin activity. Virology. 1984;137(2):314-23.
- Colman PM, Laver WG, Varghese JN, Baker AT, Tulloch PA, Air GM, Webster RG. Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature. 1987;326(6111):358-63.
- Lentz MR, Webster RG, Air GM. Site-directed mutation of the active site of influenza neuraminidase and implications for the catalytic mechanism. Biochemistry (Mosc). 1987;26(17):5351-8.
- Air GM, Laver WG. The neuraminidase of influenza virus. Proteins. 1989;6(4):341-56.
- Laver WG, Air GM, Webster RG, Smith-Gill SJ. Epitopes on protein antigens: misconceptions and realities. Cell. 1990;61(4):553-6.
- Bossart-Whitaker P, Carson M, Babu YS, Smith CD, Laver WG, Air GM. Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid. J Mol Biol. 1993;232(4):1069-83.
- Liu C, Eichelberger MC, Compans RW, Air GM. Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding. J Virol. 1995;69(2):1099-106. PMCID: 188682.
- Kumari K, Gulati S, Smith DF, Gulati U, Cummings RD, Air GM. Receptor binding specificity of recent human H3N2 influenza viruses. Virol J. 2007;4:42. PMCID: 1876801.
- Nicholls JM, Chan RW, Russell RJ, Air GM, Peiris JS. Evolving complexities of influenza virus and its receptors. Trends Microbiol. 2008;16(4):149-57.
- Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, James J, Air GM, Capra JD, Ahmed R, Wilson PC. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008;453(7195):667-71. PMCID: 2515609.
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