Chompunuch Boonarkart

Mahidol University, Bangkok, Bangkok, Thailand

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Publications (9)22.58 Total impact

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    ABSTRACT: N-linked glycosylation of the influenza virus hemagglutinin (HA) protein plays crucial roles in HA structure and function, evasion of neutralizing antibodies, and susceptibility to innate soluble antiviral factors. The N-linked glycosylation site at position 158 of highly pathogenic H5N1 virus was previously shown to affect viral receptor-binding preference. H5N1 viruses show heterogeneity with respect to the presence of this glycosylation site. Clade 1 viruses that caused outbreaks in Southeast Asia in 2004 contained this glycosylation site, while the site is absent in the more recent clade 2 viruses. Here, we show that elimination of this glycosylation site increases viral virulence in mice. The mutant lacking the glycosylation site at position 158 showed unaltered growth kinetics in vitro and a comparable level of sensitivity to a major antiviral protein found in respiratory secretions, surfactant protein D (SP-D).
    Archives of virology. 12/2014;
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    ABSTRACT: To characterise neuraminidase (NA) substrate specificity of avian influenza H5N1 strains from humans and birds comparing to seasonal influenza virus.
    World journal of virology. 11/2014; 3(4):30-6.
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    ABSTRACT: Oral cavity can be an entry site of influenza virus and saliva is known to contain innate soluble anti-influenza factors. Influenza strains were shown to vary in their susceptibility to those antiviral factors. Whether the susceptibility to the saliva antiviral factors plays any role in the host species specificity of influenza viruses is not known. In this study, the antiviral activity of human and chicken saliva against human and the H5N1 avian influenza viruses were investigated by hemagglutination inhibition (HI) and neutralization (NT) assays. In comparison to human influenza viruses, H5N1 isolates showed reduced susceptibility to human saliva as measured by HI and NT assays. Interestingly, an H5N1 isolate that bind to both α2,3- and α2,6-linked sialic acid showed much higher HI titers with human saliva, suggesting that the susceptibility profile was linked to the receptor-binding preference and the presence of α2,6-linked sialic in human saliva. On the other hand, the H5N1 isolates showed increased HI titers but reduced NT titers to chicken saliva as compared to human influenza isolates. The human salivary antiviral components were characterized by testing the sensitivity to heat, receptor destroying enzyme (RDE), CaCl2 /EDTA dependence, and inhibition by mannan, and shown to be α- and γ-inhibitors. These data suggest that the H5N1 HPAI influenza virus had distinctive susceptibility patterns to human and chicken saliva, which may play some roles in its infectivity and transmissibility in these hosts. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 11/2013; · 2.37 Impact Factor
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    ABSTRACT: We have generated a temperature-sensitive (ts) mutant from a human isolate of the H5N1 avian influenza virus by classical adaptation in cell culture. After 20 passages at low temperature, the virus showed a ts phenotype. The ts mutant also showed an attenuated phenotype after nasal inoculation in mice. Using reverse genetics, we generated reassortants carrying individual genomic segments of the wild-type and mutant viruses in an A/Puerto Rico/8/34 background, and found that the nucleoprotein (NP) gene could confer the ts phenotype. This mutant NP contains a serine-to-asparagine mutation at position 314 (S314N). The mutant NP protein showed a defect in nuclear localization at high temperature in mammalian cells.
    Archives of Virology 01/2013; · 2.28 Impact Factor
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    ABSTRACT: A case of unusually high severity of influenza pneumonia leading to acute respiratory distress syndrome and death was investigated. This was a previously a healthy 28-year-old man with no underlying conditions, admitted to a hospital during the first wave of influenza pandemic in Thailand in July 2009. He had experienced high fever and influenza-like illness for 5 days before coming to the hospital. He developed acute respiratory distress syndrome and expired on day 7 after admission. In comparison to three other cases of influenza pneumonia in the same outbreak with known risk factors for severe influenza, such as pregnancy and diabetes mellitus, a much higher viral load was detected in the lungs of this patient despite antiviral treatment. In agreement with the high viral load, the lung specimens from this patient, but not the other three patients, showed a high expression of α-2,6-linked sialic acid by lectin staining. The gene responsible for the synthesis of this sialic acid was also found to be upregulated. The data indicated overexpression of the viral receptor as a potential mechanism for severe disease in some patients.
    Journal of Medical Virology 03/2012; 84(3):380-5. · 2.37 Impact Factor
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    ABSTRACT: Microarray analysis of gene expression profile of lungs from two fatal H5N1 influenza cases identified 3,435 genes with higher than twofold changes in mRNA levels as compared to those of normal lung. One thousand nineteen genes and 2,416 genes were up-regulated and down-regulated commonly, respectively. Gene ontology analysis identified several ontology terms with significant association with these genes, most of which are related to cellular metabolism and regulation of cellular process including apoptosis and chemotaxis. Pulmonary surfactant protein D (SP-D) was found to be down-regulated. Quantitative RT-PCR confirmed the levels of SP-D mRNA in the lungs infected with H5N1 to be lower than those of normal lungs and lungs from patients with acute respiratory distress syndrome. SP-D plays multiple roles in respiratory innate defense against various pathogens, regulation of inflammatory responses, and maintenance of alveolar integrity. Reduction of SP-D in H5N1 influenza may play important roles in the pathogenesis of the disease.
    Journal of Medical Virology 08/2011; 83(8):1410-7. · 2.37 Impact Factor
  • Ornpreya Suptawiwat, Chompunuch Boonarkart, Prasert Auewarakul
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    ABSTRACT: We have previously described a cis enhancing sequence (CES) in the gp41 region of the HIV-1 env gene. It could enhance HIV-1 Gag expression via both rev-dependent and CTE (constitutive transport element)-dependent pathways. We identified a functionally important and conserved region in the CES that contained a predicted binding sequence for an SR protein, ASF/SF2. We show here that ASF/SF2 bound to this sequence in an electrophoretic mobility shift assay and that the putative ASF/SF2-binding sequence was required for the enhancement of Gag expression by CES and might play a role in HIV-1 posttranscriptional regulation.
    Archives of Virology 11/2010; 155(11):1789-95. · 2.28 Impact Factor
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    ABSTRACT: Avian influenza viruses preferentially use alpha2,3-linked sialic acid as a receptor for binding and entry into target cells. The sialic acid is the terminal residue of various types of glycan. There are two major types of alpha2,3-linked sialic acid differing in the penultimate bond: Neu5Acalpha2-3Galbeta1-3GalNAc and Neu5Acalpha2-3Galbeta1-4GlcNAc. In the human airway, while Neu5Acalpha2-3Galbeta1-3GalNAc is present only in alveolar epithelial cells, the Neu5Acalpha2-3Galbeta1-4GlcNAc is expressed in both the upper and lower airway. Previous data showed preferential binding of hemagglutinin from H5N1 highly pathogenic influenza virus to Neu5Acalpha2-3Galbeta1-4GlcNAc. We further show here that suppression of this sialic acid by siRNA against a sialyltransferase, ST3GAL4, can inhibit H5N1 avian influenza virus infection and that this gene is abundantly expressed in human pharynx, trachea and bronchus. These data suggest that the ST3GAL4 gene is responsible for biosynthesis of the viral receptor and may play a crucial role in infection of H5N1 avian influenza virus in humans.
    Archives of Virology 04/2010; 155(6):889-93. · 2.28 Impact Factor
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    ABSTRACT: Influenza viruses bind and infect respiratory epithelial cells through sialic acid on cell surface. Differential preference to sialic acid types contributes to host- and tissue-tropism of avian and seasonal influenza viruses. Although the highly pathogenic avian influenza virus H5N1 can infect and cause severe diseases in humans, it is not efficient in infecting human upper respiratory tract. This is because of the scarcity of its receptor, α2,3-linked sialic acid, in human upper airway. Expression of sialic acid can be influenced by various factors including inflammatory process. Allergic rhinitis and nasal polyp are common inflammatory conditions of nasal mucosa and may affect expression of the sialic acid and susceptibility to influenza infection. To test this hypothesis, we detected α2,3- and α2,6-linked sialic acid in human nasal polyp and normal nasal mucosal tissues by lectin staining and infected explants of those tissues with avian influenza viruses H5N1 and seasonal influenza viruses. We show here that mucosal surface of nasal polyp expressed higher level of α2,3- and α2,6-linked sialic acid than normal nasal mucosa. Accordingly, both H5N1 avian influenza viruses and seasonal influenza viruses replicated more efficiently in nasal polyp tissues explants. Our data suggest a role of nasal inflammatory conditions in susceptibility to influenza infection, especially by avian influenza viruses, which is generally inefficient in infecting human upper airway. The increased receptor expression may contribute to increased susceptibility in some individuals. This may contribute to the gradual adaptation of the virus to human population.
    PLoS ONE 01/2010; 5(9):e12973. · 3.53 Impact Factor
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    ABSTRACT: ADARs (adenosine deaminases that act on double-stranded RNA) are RNA editing enzymes that catalyze a change from adenosine to inosine, which is then recognized as guanosine by translational machinery. We demonstrate here that overexpression of ADARs but not of an ADAR mutant lacking editing activity could upregulate human immunodeficiency virus type 1 (HIV-1) structural protein expression and viral production. Knockdown of ADAR1 by RNA silencing inhibited HIV-1 production. Viral RNA harvested from transfected ADAR1-knocked-down cells showed a decrease in the level of unspliced RNA transcripts. Overexpression of ADAR1 induced editing at a specific site in the env gene, and a mutant with the edited sequence was expressed more efficiently than the wild-type viral genome. These data suggested the role of ADAR in modulation of HIV-1 replication. Our data demonstrate a novel mechanism in which HIV-1 employs host RNA modification machinery for posttranscriptional regulation of viral protein expression.
    Journal of Virology 09/2008; 82(21):10864-72. · 5.08 Impact Factor