Bioinformatics for Genomics: H275y Neuraminidase(NA)gene: Influenza Virus.

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Dr. Obumneke Amadi-Onuoha_Scripts_ 14
Bioinformatics for Genomics_CTS
06/10/2019
Hands-on Exercise: this is the graphics of bioinformatics investigation on my gene/condition of
interest. Included are snapshot from genome data analysis resources used they are, my Genome
Browser NCBI Entrez, UniProt, EMBL-EBI and Influenza Research Database with a short
narrative my gene/condition, SNPs, and others.
H275y neuraminidase (NA) gene:Influenza Virus
Influenza is a seasonalflu and an acute respiratory viral infection with capability to cause serious
complications and death, affects everyone,most at risk are the elderly and the immunocompromised
individuals. Among the most common circulating strains that infect humans is the A (H1N1) influenza
viruses (Pokorna et al, 2018, p.2). The pandemic influenza A virus that evolved with new mutation that
promoted the survival and spread of the viral strain to cause a pandemic in the year 2009. The
effectiveness of this strain was reported in many research to have initiated from a particular H275Y
mutation in the NA gene of the host cell that benefitted the host receptor binding, virulence and drug
resistance of the new virus. The H275Yis a wild-type NA,with a single mutations (Pokorna et al, 2018,
p.1). The re-assortment in the NA genome also called anti genetic drift is where distinct virus will co-
infect the same host cell and produce an offspring with mixed genome. The H275Y amino acid
substitution within the active binding site situated at the head of the NA gene confers mutation effect of
oseltamivir antiviral resistance the drug used for therapy against the virus infection in the N1 subtype of
the influenza virus(see p.13 diagram of the paper), also, the H275Y NA amino acid substitutions is
associated with reduced inhibition by NA inhibitors, have Type/subtype A(H1N1)pdm09 and A(H1N1)in
the N2 numbering(who,p.1-2). This 2009 viral neuraminidases - are EC 3.2.1.18 (exo-neuraminidases)
enzymes - use these terminal residues as their substrate (Fallon, Heil, Fallon & Szigethy, 2017, p.7) see
diagram, p.8 of the paper.
The amino acid substitution and enzymatic activity ofthe H275y NA gene:NA is an RNA protein.
NA inhibition resistance,histidine-to-tyrosine (amino acid) substitution at position 275 occurs in NA
protein. NA also, called sialidase are glycoside hydrolase enzymes that cleave the glycoproteins of
neuraminic or sialic acid to create a pathway for virus to infect other cells, this process is required for
influenza virus replication. H275Y mutation impairs NA activity and significantly reduces susceptibility
to oseltamivir, (See. Figure 1).
Gene analysis:The selected NA alignments analysis of the H275Y mutation in the seasonal
A/California/7/2009 [H1N1pdm09] and Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
background shows the changes in the infection amino acid substitution and enzymatic activity parameters.
Please, follow headings and diagrams marked in red to better help unveil further descriptions of the gene
and strains explored through the pages.

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Figure 1. Crystal structures ofmutant neuraminidase variants with oseltamivir
(Pokorna et al, 2018, p.10)

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Genomic data analysis
Describing the specified strains below to observe mutations, clinical variations, and homologs (phylogenic tree),
from annotations of nucleotides and variations alignment of the strains using the available resources:
1. UniProt
2. Influenza Research Database
3. National Center for Biotechnology Information(NCBI)
Strains:
1. Influenza A virus (A/California/07/2009(H1N1))
Sequence: NC_026434.1 (1..1410)
YP_009118627.1 neuraminidase [Influenza A virus (A/California/07/2009(H1N1))]
UniProtKB/TrEMBL : C3W6G3
Conserved Domains (1) summary : cd15483
Location:85 → 465 : Influenza_NA; Sialidase or neuraminidase (EC 3.2.1.18) of
Influenza viruses A and B
2. Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Sequence: NC_002018.1 (21..1385)
NP_040981.1 neuraminidase [Influenza A virus (A/Puerto Rico/8/1934(H1N1))]
UniProtKB/Swiss-Prot : P03468
Conserved Domains (1) summary: cd15483
Location:68 → 450 Influenza_NA; Sialidase or neuraminidase (EC 3.2.1.18) of Influenza viruses
A and B

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NCBI GENE GRAPHICS

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NA Domain specific Hits: Influenza A virus (A/California/07/2009(H1N1))
and A/Puerto Rico/8/1934(N1)

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Na Function
Na Function are similar for both organisms in Influenza virus A/California/07/2009(H1N1) and strain
Influenza virus A/Puerto Rico/8/1934 H1N1. Both have the same conserved protein domain family :
cd15483: Influenza_NA .

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Influenza Strain Details for (A/California/07/2009(H1N1))

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Influenza Strain Details for A/Puerto Rico/8/1934(N1)

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SNPs from identical nucleotide sequences:
A/California/07/2009 and A/Puerto Rico/8/1934 H1N1
Influenza A virus (A/Bethesda/NIH107-
D31/2009(H1N1))segment 6 neuraminidase (NA)
gene, complete cds

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Sequence multiple alignment

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PHYLOGENEIC TREE shows homolog between the compared strains (see diagram below)

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Reference
Fallon, J. M., Heil, M., Fallon, J., & Szigethy, J. (2017). U.S. Patent Application No. 15/265,620
Pokorná, J., Pachl, P., Karlukova, E., Hejdánek, J., Řezáčová, P., Machara, A., ... & Kožíšek,
M.(2018). Kinetic, thermodynamic, and structural analysis of drug resistance mutations
in neuraminidase from the 2009 Pandemic Influenza Virus. Viruses, 10(7), 339.
WHO (2018). Summary of neuraminidase amino acid substitutions associated with reduced
inhibition by neuraminidase inhibitors. Retrieved from
https://www.who.int/influenza/gisrs_laboratory/antiviral_susceptibility/NAI_Reduced_S
usceptibility_Marker_Table_WHO.pdf?ua=1