Displaying publications 21 - 40 of 80 in total

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  1. Hoh BP, Umi-Shakina H, Zuraihan Z, Zaiharina MZ, Rafidah-Hanim S, Mahiran M, et al.
    Hum Immunol, 2015 Jun;76(6):421-6.
    PMID: 25858769 DOI: 10.1016/j.humimm.2015.03.019
    Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P<0.05); while variants of CXCL11 showed moderate significance of association (P=0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, "CCCCA" of gene CXCL10 and "AGTTTAC" of CXCL11 were found to be significantly associated with vascular leakage (P=0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection.
    Matched MeSH terms: Dengue Virus/immunology
  2. Chem YK, Chua KB, Malik Y, Voon K
    Trop Biomed, 2015 Jun;32(2):344-51.
    PMID: 26691263 MyJurnal
    Monoclonal antibody-escape variant of dengue virus type 1 (MabEV DEN-1) was discovered and isolated in an outbreak of dengue in Klang Valley, Malaysia from December 2004 to March 2005. This study was done to investigate whether DEN152 (an isolate of MabEV DEN-1) is a product of recombination event or not. In addition, the non-synonymous mutations that correlate with the monoclonal antibody-escape variant were determined in this study. The genomes of DEN152 and two new DEN-1 isolates, DENB04 and DENK154 were completely sequenced, aligned, and compared. Phylogenetic tree was plotted and the recombination event on DEN152 was investigated. DEN152 is sub-grouped under genotype I and is closely related genetically to a DEN-1 isolated in Japan in 2004. DEN152 is not a recombinant product of any parental strains. Four amino acid substitutions were unique only to DEN 152. These amino acid substitutions were (Ser)[326](Leu), (Ser)[340](Leu) at the deduced E protein, (Ile)[250](Thr) at NS1 protein, and (Thr)[41](Ser) at NS5 protein. Thus, DEN152 is an isolate of the emerging monoclonal antibody-escape variant DEN-1 that escaped diagnostic laboratory detection.
    Matched MeSH terms: Dengue Virus/immunology*
  3. Ngim CF, Husain SMT, Hassan SS, Dhanoa A, Ahmad SAA, Mariapun J, et al.
    PLoS Negl Trop Dis, 2021 05;15(5):e0009445.
    PMID: 34014983 DOI: 10.1371/journal.pntd.0009445
    BACKGROUND: Dengue fever is the most common mosquito-borne infection worldwide where an expanding surveillance and characterization of this infection are needed to better inform the healthcare system. In this surveillance-based study, we explored the prevalence and distinguishing features of dengue fever amongst febrile patients in a large community-based health facility in southern peninsular Malaysia.

    METHODS: Over six months in 2018, we recruited 368 adults who met the WHO 2009 criteria for probable dengue infection. They underwent the following blood tests: full blood count, dengue virus (DENV) rapid diagnostic test (RDT), ELISA (dengue IgM and IgG), nested RT-PCR for dengue, multiplex qRT-PCR for Zika, Chikungunya and dengue as well as PCR tests for Leptopspira spp., Japanese encephalitis and West Nile virus.

    RESULTS: Laboratory-confirmed dengue infections (defined by positive tests in NS1, IgM, high-titre IgG or nested RT-PCR) were found in 167 (45.4%) patients. Of these 167 dengue patients, only 104 (62.3%) were positive on rapid diagnostic testing. Dengue infection was significantly associated with the following features: family or neighbours with dengue in the past week (AOR: 3.59, 95% CI:2.14-6.00, p<0.001), cutaneous rash (AOR: 3.58, 95% CI:1.77-7.23, p<0.001), increased temperature (AOR: 1.33, 95% CI:1.04-1.70, p = 0.021), leucopenia (white cell count < 4,000/μL) (AOR: 3.44, 95% CI:1.72-6.89, p<0.001) and thrombocytopenia (platelet count <150,000/μL)(AOR: 4.63, 95% CI:2.33-9.21, p<0.001). Dengue infection was negatively associated with runny nose (AOR: 0.47, 95% CI:0.29-0.78, p = 0.003) and arthralgia (AOR: 0.42, 95% CI:0.24-0.75, p = 0.004). Serotyping by nested RT-PCR revealed mostly mono-infections with DENV-2 (n = 64), DENV-1 (n = 32) and DENV-3 (n = 17); 14 co-infections occurred with DENV-1/DENV-2 (n = 13) and DENV-1/DENV-4 (n = 1). Besides dengue, none of the pathogens above were found in patients' serum.

    CONCLUSIONS: Acute undifferentiated febrile infections are a diagnostic challenge for community-based clinicians. Rapid diagnostic tests are increasingly used to diagnose dengue infection but negative tests should be interpreted with caution as they fail to detect a considerable proportion of dengue infection. Certain clinical features and haematological parameters are important in the clinical diagnosis of dengue infection.

    Matched MeSH terms: Dengue Virus/immunology*
  4. Zainal N, Tan KK, Johari J, Hussein H, Wan Musa WR, Hassan J, et al.
    Microbiol. Immunol., 2018 Oct;62(10):659-672.
    PMID: 30259549 DOI: 10.1111/1348-0421.12652
    Dengue is the most prevalent mosquito-borne disease in Southeast Asia, where the incidence of systemic lupus erythematosus (SLE) is approximately 30 to 53 per 100,000. Severe dengue, however, is rarely reported among individuals with SLE. Here, whether sera of patients with SLE cross-neutralize dengue virus (DENV) was investigated. Serum samples were obtained from individuals with SLE who were dengue IgG and IgM serology negative. Neutralization assays were performed against the three major DENV serotypes. Of the dengue serology negative sera of individuals with SLE, 60%, 61% and 52% of the sera at 1/320 dilution showed more than 50% inhibition against dengue type-1 virus (DENV-1), DENV-2 and DENV-3, respectively. The neutralizing capacity of the sera was significantly greater against DENV-1 (P 
    Matched MeSH terms: Dengue Virus/immunology*
  5. Suppiah J, Ching SM, Amin-Nordin S, Mat-Nor LA, Ahmad-Najimudin NA, Low GK, et al.
    PLoS Negl Trop Dis, 2018 09;12(9):e0006817.
    PMID: 30226880 DOI: 10.1371/journal.pntd.0006817
    BACKGROUND: Malaysia experienced an unprecedented dengue outbreak from the year 2014 to 2016 that resulted in an enormous increase in the number of cases and mortality as compared to previous years. The causes that attribute to a dengue outbreak can be multifactorial. Viral factors, such as dengue serotype and genotype, are the components of interest in this study. Although only a small number of studies investigated the association between the serotype of dengue virus and clinical manifestations, none of these studies included analyses on dengue genotypes. The present study aims to investigate dengue serotype and genotype-specific clinical characteristics among dengue fever and severe dengue cases from two Malaysian tertiary hospitals between 2014 and mid-2017.

    METHODOLOGY AND PRINCIPAL FINDINGS: A total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients' clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia.

    CONCLUSION: The current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients.

    Matched MeSH terms: Dengue Virus/immunology
  6. Jahanshahi P, Wei Q, Jie Z, Ghomeishi M, Sekaran SD, Mahamd Adikan FR
    Bioengineered, 2017 May 04;8(3):239-247.
    PMID: 27533620 DOI: 10.1080/21655979.2016.1223413
    Surface plasmon resonance (SPR) sensing is recently emerging as a valuable technique for measuring the binding constants, association and dissociation rate constants, and stoichimetry for a binding interaction kinetics in a number of emerging biological areas. This technique can be applied to the study of immune system diseases in order to contribute to improved understanding and evaluation of binding parameters for a variety of interactions between antigens and antibodies biochemically and clinically. Since the binding constants determination of an anti-protein dengue antibody (Ab) to a protein dengue antigen (Ag) is mostly complicated, the SPR technique aids a determination of binding parameters directly for a variety of particular dengue Ag_Ab interactions in the real-time. The study highlights the doctrine of real-time dengue Ag_Ab interaction kinetics as well as to determine the binding parameters that is performed with SPR technique. In addition, this article presents a precise prediction as a reference curve for determination of dengue sample concentration.
    Matched MeSH terms: Dengue Virus/immunology*
  7. Chan SY, Kautner IM, Lam SK
    J Virol Methods, 1994 Oct;49(3):315-22.
    PMID: 7868649
    The potential of RT-PCR to rapidly diagnose dengue infections from both acute and convalescent phase patients' sera was evaluated. The RNA extraction method involved binding of the viral RNA to silica particles in the presence of high concentration of guanidine thiocyanate. The protocol that was established was sensitive enough to detect 40 plaque forming units per 100 microliter of serum and results could be obtained within one day. Results from this study indicate that clinical samples should be collected in the early acute phase of illness when anti-dengue antibodies were undetectable or of low titres to ensure a more reliable diagnosis.
    Matched MeSH terms: Dengue Virus/immunology
  8. Dhanoa A, Hassan SS, Jahan NK, Reidpath DD, Fatt QK, Ahmad MP, et al.
    Infect Dis Poverty, 2018 Jan 16;7(1):1.
    PMID: 29335021 DOI: 10.1186/s40249-017-0384-1
    BACKGROUND: The frequency and magnitude of dengue epidemics continue to increase exponentially in Malaysia, with a shift in the age range predominance toward adults and an expansion to rural areas. Despite this, information pertaining to the extent of transmission of dengue virus (DENV) in the rural community is lacking. This community-based pilot study was conducted to establish DENV seroprevalence amongst healthy adults in a rural district in Southern Malaysia, and to identify influencing factors.

    METHODS: In this study undertaken between April and May 2015, a total of 277 adult participants were recruited from households across three localities in the Sungai Segamat subdistrict in Segamat district. Sera were tested for immunoglobulin G (IgG) (Panbio® Dengue Indirect IgG ELISA/high-titer capture) and immunoglobulin M (IgM) (Panbio®) antibodies. The plaque reduction neutralization test (PRNT) was conducted on random samples of IgG-positive sera for further confirmation. Medical history and a recall of previous history of dengue were collected through interviews, whereas sociodemographic information was obtained from an existing database.

    RESULTS: The overall seroprevalence for DENV infection was 86.6% (240/277) (95% CI: 83-91%). Serological evidence of recent infection (IgM/high-titer capture IgG) was noted in 11.2% (31/277) of participants, whereas there was evidence of past infection in 75.5% (209/277) of participants (indirect IgG minus recent infections). The PRNT assay showed that the detected antibodies were indeed specific to DENV. The multivariate analysis showed that the older age group was significantly associated with past DENV infections. Seropositivity increased with age; 48.5% in the age group of <25 years to more than 85% in age group of >45 years (P 

    Matched MeSH terms: Dengue Virus/immunology*
  9. Teoh PG, Ooi AS, AbuBakar S, Othman RY
    J Biomed Biotechnol, 2009;2009:781712.
    PMID: 19325913 DOI: 10.1155/2009/781712
    A Cucumber green mottle mosaic virus (CGMMV) was used to present a truncated dengue virus type 2 envelope (E) protein binding region from amino acids 379 to 423 (EB4). The EB4 gene was inserted at the terminal end of the CGMMV coat protein (CP) open reading frame (ORF). Read-through sequences of TMV or CGMMV, CAA-UAG-CAA-UUA, or AAA-UAG-CAA-UUA were, respectively, inserted in between the CP and the EB4 genes. The chimeric clones, pRT, pRG, and pCG+FSRTRE, were transcribed into full-length capped recombinant CGMMV transcripts. Only constructs with the wild-type CGMMV read-through sequence yielded infectious viruses following infection of host plant, muskmelon (Cucumis melo) leaves. The ratio of modified to unmodified CP for the read-through expression clone developed was also found to be approximately 1:1, higher than what has been previously reported. It was also observed that infectivity was not affected by differences in pI between the chimera and its wild counterpart. Analysis of recombinant viruses after 21-days-postinculation (dpi) revealed that deletions occurred resulting in partial reversions of the viral population to near wild type and suggesting that this would be the limiting harvest period for obtaining true to type recombinants with this construct.
    Matched MeSH terms: Dengue Virus/immunology*
  10. Appanna R, Huat TL, See LL, Tan PL, Vadivelu J, Devi S
    Clin Vaccine Immunol, 2007 Aug;14(8):969-77.
    PMID: 17567768
    Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas in the world. Attempts to develop effective vaccines have been hampered by the lack of understanding of the pathogenesis of the disease and the absence of suitable experimental models for dengue viral infection. The magnitude of T-cell responses has been reported to correlate with dengue disease severity. Sixty Malaysian adults with dengue viral infections were investigated for their dengue virus-specific T-cell responses to 32 peptides antigens from the structural and nonstructural regions from a dengue virus isolate. Seventeen different peptides from the C, E, NS2B, NS3, NS4A, NS4B, and NS5 regions were found to evoke significant responses in a gamma interferon enzyme-linked immunospot (ELISPOT) assay of samples from 13 selected patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). NS3 and predominantly NS3(422-431) were found to be important T-cell targets. The highest peaks of T-cell responses observed were in responses to NS3(422-431) and NS5(563-571) in DHF patients. We also found almost a sevenfold increase in T-cell response in three DHF patients compared to three DF patient responses to peptide NS3(422-431). A large number of patients' T cells also responded to the NS2B(97-106) region. The ELISPOT analyses also revealed high frequencies of T cells that recognize both serotype-specific and cross-reactive dengue virus antigens in patients with DHF.
    Matched MeSH terms: Dengue Virus/immunology*
  11. Chen RE, Smith BK, Errico JM, Gordon DN, Winkler ES, VanBlargan LA, et al.
    Cell Host Microbe, 2021 Nov 10;29(11):1634-1648.e5.
    PMID: 34610295 DOI: 10.1016/j.chom.2021.09.006
    Although divergent dengue viruses (DENVs) have been isolated in insects, nonhuman primates, and humans, their relationships to the four canonical serotypes (DENV 1-4) are poorly understood. One virus isolated from a dengue patient, DKE-121, falls between genotype and serotype levels of sequence divergence to DENV-4. To examine its antigenic relationship to DENV-4, we assessed serum neutralizing and protective activity. Whereas DENV-4-immune mouse sera neutralize DKE-121 infection, DKE-121-immune sera inhibit DENV-4 less efficiently. Passive transfer of DENV-4 or DKE-121-immune sera protects mice against homologous, but not heterologous, DENV-4 or DKE-121 challenge. Antigenic cartography suggests that DENV-4 and DKE-121 are related but antigenically distinct. However, DENV-4 vaccination confers protection against DKE-121 in nonhuman primates, and serum from humans immunized with a tetravalent vaccine neutralize DENV-4 and DKE-121 infection equivalently. As divergent DENV strains, such as DKE-121, may meet criteria for serotype distinction, monitoring their capacity to impact dengue disease and vaccine efficacy appears warranted.
    Matched MeSH terms: Dengue Virus/immunology*
  12. Wang SM, Sekaran SD
    J Clin Microbiol, 2010 Aug;48(8):2793-7.
    PMID: 20573879 DOI: 10.1128/JCM.02142-09
    Early definitive diagnosis of dengue virus infection may help in the timely management of dengue virus infection. We evaluated the Standard Diagnostics (SD, South Korea) dengue virus nonstructural protein NS1 antigen enzyme-linked immunosorbent assay (SD dengue NS1 Ag ELISA) for the detection of dengue virus NS1 antigen in patients' sera, using a total of 399 serum samples in a comparison with real-time reverse transcription (RT)-PCR, an in-house IgM capture (MAC)-ELISA, and a hemagglutination inhibition (HI) assay. Of the 320 dengue sera, 205 (64%) tested positive for NS1 antigen compared to 300 (93.75%) by either MAC-ELISA or RT-PCR, 161 (50.31%) by RT-PCR, and 226 (70.36%) by MAC-ELISA only. The assay was able to detect NS1 antigen in convalescent-phase sera until day 14 of infection. The NS1 detection rate is inversely proportional while the IgM detection rate is directly proportional to the presence of IgG antibodies. The overall sensitivity and specificity of the SD dengue NS1 Ag ELISA in the detection of "confirmed dengue virus" sera are 76.76% and 98.31%, respectively. This suggests that the SD kit is highly specific and sensitive for the detection of NS1 antigen. However, caution is needed when the kit is used as a single assay, as detection in samples that contained the virus was only about 81.97%. Combining this assay with an IgM and/or IgG assay will increase the sensitivity of detection, especially in areas with a higher prevalence of secondary dengue virus infections.
    Matched MeSH terms: Dengue Virus/immunology
  13. Mohamed Ismail NA, Wan Abd Rahim WE, Salleh SA, Neoh HM, Jamal R, Jamil MA
    ScientificWorldJournal, 2014;2014:436975.
    PMID: 25587564 DOI: 10.1155/2014/436975
    Malaysia a dengue endemic country with dengue infections in pregnancy on the rise. The present study was aimed at determining dengue seroprevalence (IgG or IgM) during pregnancy and its neonatal transmission in dengue seropositive women.
    Matched MeSH terms: Dengue Virus/immunology*
  14. Yang F, Guo GZ, Chen JQ, Ma HW, Liu T, Huang DN, et al.
    Epidemiol Infect, 2014 Feb;142(2):225-33.
    PMID: 23587429 DOI: 10.1017/S0950268813000897
    A suspected dengue fever outbreak occurred in 2010 at a solitary construction site in Shenzhen city, China. To investigate this epidemic, we used serological, molecular biological, and bioinformatics techniques. Of nine serum samples from suspected patients, we detected seven positive for dengue virus (DENV) antibodies, eight for DENV-1 RNA, and three containing live viruses. The isolated virus, SZ1029 strain, was sequenced and confirmed as DENV-1, showing the highest E-gene homology to D1/Malaysia/36000/05 and SG(EHI)DED142808 strains recently reported in Southeast Asia. Further phylogenetic tree analysis confirmed their close relationship. At the epidemic site, we also detected 14 asymptomatic co-workers (out of 291) positive for DENV antibody, and DENV-1-positive mosquitoes. Thus, we concluded that DENV-1 caused the first local dengue fever outbreak in Shenzhen. Because no imported case was identified, the molecular fingerprints of the SZ1029 strain suggest this outbreak may be due to vertical transmission imported from Southeast Asia.
    Matched MeSH terms: Dengue Virus/immunology
  15. Chen WS, Wong CH, Cillekens L
    Med J Malaysia, 2003 Mar;58(1):142-3.
    PMID: 14556343
    Matched MeSH terms: Dengue Virus/immunology*
  16. Wallace HG, Lim TW, Rudnick A, Knudsen AB, Cheong WH, Chew V
    PMID: 6105712
    The first major Malaysian epidemic of dengue hemorrhagic fever with severe manifestations occurred in 1973, with 969 reported cases and 54 deaths. In a detailed study of 138 clinically diagnosed and laboratory confirmed cases at the General Hospital in Kuala Lumpur, hemorrhagic manifestations were observed in 68.7% and shock in 18.1% of the patients. The cases occurred mainly from May to September, largely in urban and suburban areas of the majority of the states in the country. A main focus of infection was Jinjang, a heavily populated outlying district of Kuala Lumpur, where unusually high incidences of morbidity, severe disease and mortality were seen. Severe disease was seen mostly in children under the age of 15 years, although a significant number of adults suffered milder illnesses. The Chinese population was chiefly affected, due to their living in crowded, low-income housing where the vector, Aedes aegypti, occurred in the greatest numbers. All four dengue types were recovered during the epidemic period, although dengue 3 (DEN-3) was incriminated as the major epidemic type. Entomological data revealed high indices of A. aegypti throughout the country and left little doubt that this epidemic was aegypti transmitted. Spraying and fogging operations were carried out in attempts to control vector populations.
    Matched MeSH terms: Dengue Virus/immunology
  17. Pang T
    Ann Acad Med Singap, 1987 Oct;16(4):612-6.
    PMID: 2895602
    Studies were carried out into the immunopathogenesis and laboratory diagnosis of dengue virus infections. Using an experimental system it was shown that cell-mediated immunity (CMI), as measured by delayed-type hypersensitivity (DTH) was induced in mice infected with dengue virus. The nature of the DTH response satisfies most criteria for a classical DTH reaction. In addition, it was also shown that infection with dengue virus causes a transient immunosuppression as measured by the immune response to other, unrelated antigens. With regard to the laboratory diagnosis of dengue infections, it was found that mosquito cells were a sensitive system for the isolation of dengue viruses and that the success of isolation was related to the antibody content of the serum. A new method for the rapid isolation of dengue viruses was also developed involving the intracerebral inoculation of mosquito larvae. By the use of this method viral antigens can be detected as early as 2-3 days after specimen inoculation. The significance of these findings in relation to the immunopathogenesis, prevention and control of disease syndromes due to dengue viruses is discussed.
    Matched MeSH terms: Dengue Virus/immunology
  18. Chinikar S, Ghiasi SM, Shah-Hosseini N, Mostafavi E, Moradi M, Khakifirouz S, et al.
    Travel Med Infect Dis, 2013 May-Jun;11(3):166-9.
    PMID: 23194952 DOI: 10.1016/j.tmaid.2012.10.001
    Dengue fever is one of the most important arthropod-borne viral diseases of public health significance. It is endemic in most tropical and subtropical parts of the world, many of which are popular tourist destinations. The presence of dengue infection was examined in Iranian patients who were referred to the Arboviruses and Viral Haemorrhagic Fevers Laboratory of the Pasteur Institute of Iran and tested negative for Crimean-Congo Haemorrhagic Fever (CCHF) between 2000 and 2012. Serum samples from these patients were tested for the presence of specific IgG and IgM and viral nucleic acid in blood. Of the 300 sera tested, 15 (5%) were seropositive, and 3 (1%) were both serologically and PCR positive. Of the 15 seropositive cases, 8 (53.3%) had travelled to endemic areas including Malaysia (5, 62.5%), India (2, 25%) and Thailand (1, 12.5%). In contrast, 7 (46.7%) of the cases had not reported travelling abroad. Of these, six cases were from the Sistan and Baluchistan province in southeast Iran and neighbouring Pakistan. Travellers play a key role in the epidemiology of dengue infection in Iran and it is recommended that travellers to endemic areas take precautionary measures to avoid mosquito bites.
    Matched MeSH terms: Dengue Virus/immunology
  19. Othman S, Rahman NA, Yusof R
    Virus Res, 2012 Jan;163(1):238-45.
    PMID: 22001567 DOI: 10.1016/j.virusres.2011.09.040
    Despite aggressive efforts in dengue research, the control of dengue diseases and discovery of therapeutics against them await complete elucidation of its complex immune-pathogenesis. Unlike many viruses that escape the host's immune responses by suppressing the major histocompatibility complex (MHC) Class I pathway, many Flaviviruses up-regulate the cell surface expression of MHC Class I complex. We recently reported MHC Class I HLA-A2 promoter activation by all serotypes of dengue virus (DV). The mechanism by which DV regulates this is further explored here in HepG2 human liver cell line. Using real-time PCR, evidence that, similar to infections by other Flaviviruses, DV infection has the ability to up-regulate the MHC Class I transcription and mRNA synthesis, is presented. The region responsive towards DV infection of all serotypes was mapped to the Class I Regulatory Complex (CRC) of the HLA-A2 promoter. Competition electrophoretic mobility shift assay (EMSA) with NFκB probe established the presence of specific DNA-protein complex in DV-infected nuclear extracts. Antibody-supershift assays identified the MHC Class I promoter activation by DV to occur through binding of p65/p50 heterodimers and p65 homodimers to κB1 and κB2 cis-acting elements, respectively, within the CRC, and not with the interferon consensus sequence (ICS). This study presents evidence of MHC Class I gene modulation by DV, hence providing a better understanding of dengue immune-pathogenesis that would consequently facilitate the discovery of antiviral therapeutics against dengue.
    Matched MeSH terms: Dengue Virus/immunology*
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