TY - JOUR
T1 - Characteristics of influenza HA-NA interdependence determined through a graphical technique
AU - Nandy, Ashesh
AU - Sarkar, Tapati
AU - Basak, Subhash C.
AU - Nandy, Papiya
AU - Das, Sukhen
PY - 2014
Y1 - 2014
N2 - Influenza viruses are characterized by two surface proteins - the hemagglutinin (HA) of which there are 16 varieties, and the neuraminidase (NA) of which there are 9, each subtype characterized by its antigenic properties. Although theoretically 16 x 9 combinations are possible, only a few like the H1N1, H3N2, etc are seen to occur more frequently. Numerous studies with select subtypes like H1N1, H5N1, etc., have explained this phenomena by indicating that viral viability necessitates functional balance between the NA and HA so that only some combinations are favored. However, the reasons for this balance or its characteristics and whether this is universal for influenza subtypes are not yet known. Using novel graphical techniques and hypothesizing a coupling between the HA and NA, we devised a coupling factor to estimate the interdependence, if any, between HA and NA sequences covering a global sample of 10 subtypes and 164 sequences. We found that (a) the coupling we hypothesized between HAs and NAs is characteristic of each subtype, (b) within each subtype the coupling value is significantly different for human infecting strains and those that infect avians, and (c) artificial strains made up by mixing and matching HAs and NAs from different subtypes produce coupling factors that are far from the characteristic values for the parent subtype indicating possibly non-viable viruses, a result that matches with experimental evidence of Zhang et al. [1]. We also show that some natural strains that did not fit the characteristic values for its subtype could have been possible mismatches during viral packaging. Our observations have important consequences for drug and vaccine design and for monitoring of influenza virus reassortments and possible evolution of human pandemics.
AB - Influenza viruses are characterized by two surface proteins - the hemagglutinin (HA) of which there are 16 varieties, and the neuraminidase (NA) of which there are 9, each subtype characterized by its antigenic properties. Although theoretically 16 x 9 combinations are possible, only a few like the H1N1, H3N2, etc are seen to occur more frequently. Numerous studies with select subtypes like H1N1, H5N1, etc., have explained this phenomena by indicating that viral viability necessitates functional balance between the NA and HA so that only some combinations are favored. However, the reasons for this balance or its characteristics and whether this is universal for influenza subtypes are not yet known. Using novel graphical techniques and hypothesizing a coupling between the HA and NA, we devised a coupling factor to estimate the interdependence, if any, between HA and NA sequences covering a global sample of 10 subtypes and 164 sequences. We found that (a) the coupling we hypothesized between HAs and NAs is characteristic of each subtype, (b) within each subtype the coupling value is significantly different for human infecting strains and those that infect avians, and (c) artificial strains made up by mixing and matching HAs and NAs from different subtypes produce coupling factors that are far from the characteristic values for the parent subtype indicating possibly non-viable viruses, a result that matches with experimental evidence of Zhang et al. [1]. We also show that some natural strains that did not fit the characteristic values for its subtype could have been possible mismatches during viral packaging. Our observations have important consequences for drug and vaccine design and for monitoring of influenza virus reassortments and possible evolution of human pandemics.
KW - Drug and vaccine development
KW - Graphical representation
KW - HA sequence plots
KW - HA-NA coupling characteristics
KW - HA-NA interdependence
KW - Mathematical characterization
KW - Monitoring flu sequences
KW - NA sequence plots
UR - http://www.scopus.com/inward/record.url?scp=84946909507&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946909507&partnerID=8YFLogxK
U2 - 10.2174/1573409911666150318203621
DO - 10.2174/1573409911666150318203621
M3 - Article
C2 - 25794303
AN - SCOPUS:84930592599
VL - 10
SP - 285
EP - 302
JO - Current Computer-Aided Drug Design
JF - Current Computer-Aided Drug Design
SN - 1573-4099
IS - 4
ER -