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Fulltext Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes

Lee CY, Huang CH, Rastegari E, Rengganaten V, Liu PC, Tsai PH, et al.

Int J Mol Sci, 2021 Sep 13;22(18).
PMID: 34576032 DOI: 10.3390/ijms22189869

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.

Matched MeSH terms: Cardiovascular Diseases/virology; Myocytes, Cardiac/virology
Fulltext Middle East Respiratory Syndrome (MERS) Virus-Pathophysiological Axis and the Current Treatment Strategies

Alnuqaydan AM, Almutary AG, Sukamaran A, Yang BTW, Lee XT, Lim WX, et al.

AAPS PharmSciTech, 2021 Jun 08;22(5):173.
PMID: 34105037 DOI: 10.1208/s12249-021-02062-2

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.

Matched MeSH terms: Camels/virology; Chiroptera/virology
Fulltext Genetic diversity of Coxsackievirus A21 associated with sporadic cases of acute respiratory infections in Malaysia

Supian NI, Ng KT, Chook JB, Takebe Y, Chan KG, Tee KK

BMC Infect Dis, 2021 May 17;21(1):446.
PMID: 34001016 DOI: 10.1186/s12879-021-06148-x

BACKGROUND: Coxsackievirus A21 (CVA21), a member of Enterovirus C from the Picornaviridae family, has been associated with respiratory illnesses in humans.
METHODS: A molecular epidemiological investigation of CVA21 was conducted among patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014 in Kuala Lumpur, Malaysia.
RESULTS: Epidemiological surveillance of acute respiratory infections (n = 3935) showed low-level detection of CVA21 (0.08%, 1.4 cases/year) in Kuala Lumpur, with no clear seasonal distribution. Phylogenetic analysis of the new complete genomes showed close relationship with CVA21 strains from China and the United States. Spatio-temporal mapping of the VP1 gene determined 2 major clusters circulating worldwide, with inter-country lineage migration and strain replacement occurring over time.
CONCLUSIONS: The study highlights the emerging role of CVA21 in causing sporadic acute respiratory outbreaks.

Matched MeSH terms: Coxsackievirus Infections/virology; Respiratory Tract Infections/virology
Knowledge, attitude and practice of malaysian medical and pharmacy students towards human papillomavirus vaccination

Rashwan HH, Saat NZ, Abd Manan DN

Asian Pac J Cancer Prev, 2012;13(5):2279-83.
PMID: 22901207

Human Papillomavirus (HPV) infection is one of the most common sexually transmitted infections and oncogenic HPV is the main cause of cervical cancer. However, HPV vaccination is already available as the primary preventive method against cervical cancer. The objective of this study was to determine the level of knowledge, attitude and practice of HPV vaccination among Universiti Kebangsaan Malaysia (UKM) and Universiti Malaya (UM) students. This study was conducted from March until August 2009. Pre-tested and validated questionnaires were filled by the third year UKM (n=156) and UM (n=149) students from medical, dentistry and pharmacy faculties. The results showed that the overall level of knowledge on HPV infection, cervical cancer and its prevention among respondents was high and the majority of them had positive attitude towards HPV vaccination. Medical students had the highest level of knowledge (p<0.05). Very few students (3.6%) had already taken the vaccine with no significant difference between the two Universities (p=0.399). In conclusion, the knowledge and attitude of the respondents were high and positive, respectively. Only few students took HPV vaccination. Thus, more awareness campaigns and HPV vaccination services should be provided at universities' campuses with the price of the HPV vaccine reduced for the students.

Matched MeSH terms: Uterine Cervical Neoplasms/virology; Papillomavirus Infections/virology
Clinical significance of plasma Epstein-Barr Virus DNA loads in a large cohort of Malaysian patients with nasopharyngeal carcinoma

Chai SJ, Pua KC, Saleh A, Yap YY, Lim PV, Subramaniam SK, et al.

J Clin Virol, 2012 Sep;55(1):34-9.
PMID: 22739102 DOI: 10.1016/j.jcv.2012.05.017

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia.

Matched MeSH terms: Nasopharyngeal Neoplasms/virology*; Epstein-Barr Virus Infections/virology*
Fulltext Investigation of a potential zoonotic transmission of orthoreovirus associated with acute influenza-like illness in an adult patient

Chua KB, Voon K, Yu M, Keniscope C, Abdul Rasid K, Wang LF

PLoS One, 2011;6(10):e25434.
PMID: 22022394 DOI: 10.1371/journal.pone.0025434

Bats are increasingly being recognized as important reservoir hosts for a large number of viruses, some of them can be highly virulent when they infect human and livestock animals. Among the new bat zoonotic viruses discovered in recent years, several reoviruses (respiratory enteric orphan viruses) were found to be able to cause acute respiratory infections in humans, which included Melaka and Kampar viruses discovered in Malaysia, all of them belong to the genus Orthoreovirus, family Reoviridae. In this report, we describe the isolation of a highly related virus from an adult patient who suffered acute respiratory illness in Malaysia. Although there was no direct evidence of bat origin, epidemiological study indicated the potential exposure of the patient to bats before the onset of disease. The current study further demonstrates that spillover events of different strains of related orthoreoviruses from bats to humans are occurring on a regular basis, which calls for more intensive and systematic surveillances to fully assess the true public health impact of these newly discovered bat-borne zoonotic reoviruses.

Matched MeSH terms: Influenza, Human/virology*; Zoonoses/virology*
RNA-binding region of Macrobrachium rosenbergii nodavirus capsid protein

Goh ZH, Mohd NAS, Tan SG, Bhassu S, Tan WS

J Gen Virol, 2014 Sep;95(Pt 9):1919-1928.
PMID: 24878641 DOI: 10.1099/vir.0.064014-0

White tail disease (WTD) kills prawn larvae and causes drastic losses to the freshwater prawn (Macrobrachium rosenbergii) industry. The main causative agent of WTD is Macrobrachium rosenbergii nodavirus (MrNV). The N-terminal end of the MrNV capsid protein is very rich in positively charged amino acids and is postulated to interact with RNA molecules. N-terminal and internal deletion mutagenesis revealed that the RNA-binding region is located at positions 20-29, where 80 % of amino acids are positively charged. Substitution of all these positively charged residues with alanine abolished the RNA binding. Mutants without the RNA-binding region still assembled into virus-like particles, suggesting that this region is not a part of the capsid assembly domain. This paper is, to the best of our knowledge, the first to report the specific RNA-binding region of MrNV capsid protein.

Matched MeSH terms: Capsid/virology; Palaemonidae/virology
Fulltext Laboratory-confirmed case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Malaysia: preparedness and response, April 2014

Premila Devi J, Noraini W, Norhayati R, Chee Kheong C, Badrul AS, Zainah S, et al.

Euro Surveill, 2014 May 08;19(18).
PMID: 24832116

On 14 April 2014, the first laboratory-confirmed case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported in Malaysia in a man in his mid-fifties, who developed pneumonia with respiratory distress, after returning from a pilgrimage to Saudi Arabia. The case succumbed to his illness three days after admission at a local hospital. The follow-up of 199 close contacts identified through contact tracing and vigilant surveillance did not result in detecting any other confirmed cases of MERS-CoV infection.

Matched MeSH terms: Respiratory Tract Infections/virology; Coronavirus Infections/virology
Fulltext Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge

Yoneda M, Georges-Courbot MC, Ikeda F, Ishii M, Nagata N, Jacquot F, et al.

PLoS One, 2013;8(3):e58414.
PMID: 23516477 DOI: 10.1371/journal.pone.0058414

Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G). Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi). Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.

Matched MeSH terms: Brain/virology; Lung/virology
Fulltext Transmission routes for nipah virus from Malaysia and Bangladesh

Clayton BA, Middleton D, Bergfeld J, Haining J, Arkinstall R, Wang L, et al.

Emerg Infect Dis, 2012 Dec;18(12):1983-93.
PMID: 23171621 DOI: 10.3201/eid1812.120875

Human infections with Nipah virus in Malaysia and Bangladesh are associated with markedly different patterns of transmission and pathogenicity. To compare the 2 strains, we conducted an in vivo study in which 2 groups of ferrets were oronasally exposed to either the Malaysia or Bangladesh strain of Nipah virus. Viral shedding and tissue tropism were compared between the 2 groups. Over the course of infection, significantly higher levels of viral RNA were recovered from oral secretions of ferrets infected with the Bangladesh strain. Higher levels of oral shedding of the Bangladesh strain of Nipah virus might be a key factor in onward transmission in outbreaks among humans.

Matched MeSH terms: Ferrets/virology; Henipavirus Infections/virology
Detection and differentiation of velogenic and lentogenic Newcastle disease viruses using SYBR Green I real-time PCR with nucleocapsid gene-specific primers

Tan SW, Ideris A, Omar AR, Yusoff K, Hair-Bejo M

J Virol Methods, 2009 Sep;160(1-2):149-56.
PMID: 19447142 DOI: 10.1016/j.jviromet.2009.05.006

SYBR Green I real-time PCR was developed for detection and differentiation of Newcastle disease virus (NDV). Primers based on the nucleocapsid (NP) gene were designed to detect specific sequence of velogenic strains and lentogenic/vaccine strains, respectively. The assay was developed and tested with NDV strains which were characterized previously. The velogenic strains were detected only by using velogenic-specific primers with a threshold cycle (C(t)) 18.19+/-3.63 and a melting temperature (T(m)) 86.0+/-0.28 degrees C. All the lentogenic/vaccine strains, in contrast, were detected only when lentogenic-specific primers were used, with the C(t) value 14.70+/-2.32 and T(m) 87.4+/-0.21 degrees C. The assay had a dynamic detection range which spans over a 5log(10) concentration range, 10(9)-10(5) copies of DNA plasmid/reaction. The velogenic and lentogenic amplifications showed high PCR efficiency of 100% and 104%, respectively. The velogenic and lentogenic amplifications were highly reproducible with assay variability 0.45+/-0.31% and 1.30+/-0.65%, respectively. The SYBR Green I real-time PCR assay detected successfully the virus from tissue samples and oral swabs collected from the velogenic and lentogenic NDV experimental infection, respectively. In addition, the assay detected and differentiated accurately NDV pathotypes from suspected field samples where the results were in good agreement with both virus isolation and analysis of the fusion (F) cleavage site sequence. The assay offers an attractive alternative method for the diagnosis of NDV.

Matched MeSH terms: Bird Diseases/virology; Newcastle Disease/virology
Development of SYBR green I based one-step real-time RT-PCR assay for the detection and differentiation of very virulent and classical strains of infectious bursal disease virus

Kong LL, Omar AR, Hair Bejo M, Ideris A, Tan SW

J Virol Methods, 2009 Nov;161(2):271-9.
PMID: 19591873 DOI: 10.1016/j.jviromet.2009.06.023

A SYBR Green I based one-step real-time reverse transcriptase polymerase chain reaction was developed for the detection and differentiation of very virulent (vv) and classical strains of infectious bursal disease virus (IBDV). The assay showed high PCR efficiency >93% and high reproducibility with coefficient of variation less than 0.5%. When tested on characterized IBDV strains, the very virulent and classical-specific primers detected accurately only vvIBDV and classical IBDV strains, respectively. The diagnostic efficacy of the assay was also tested on 140 bursal samples from experimental infection and 37 bursal samples from cases suspected of IBD. The assay was able to detect IBDV from bursal samples collected at days 3 and 5 post-infection with the vvIBDV strain UPM94/273 and the classical IBDV strain D78. The assay was also able to detect bursal samples infected dually with D78 and UPM94/273. The melting temperature values of the amplification products from the classical and very virulent viral infection were statistically significant (P<0.05). The specificity of the assay for detecting IBDV from suspected cases was confirmed by sequence analysis of the VP2 gene. The assay showed high sensitivity since bursal samples which were negative for IBDV were confirmed by virus isolation and PCR amplification. Hence, the new assay offers an attractive method for rapid detection of strains of IBDV.

Matched MeSH terms: Bursa of Fabricius/virology; Birnaviridae Infections/virology
Feline parvovirus infection in an Asian palm civet (Paradoxurus hermaphroditus)

Demeter Z, Gál J, Palade EA, Rusvai M

Vet Rec, 2009 Feb 14;164(7):213-6.
PMID: 19218594
Matched MeSH terms: Feline Panleukopenia/virology*; Intestine, Small/virology
Production of the matrix protein of Nipah virus in Escherichia coli: virus-like particles and possible application for diagnosis

Subramanian SK, Tey BT, Hamid M, Tan WS

J Virol Methods, 2009 Dec;162(1-2):179-83.
PMID: 19666056 DOI: 10.1016/j.jviromet.2009.07.034

The broad species tropism of Nipah virus (NiV) coupled with its high pathogenicity demand a rapid search for a new biomarker candidate for diagnosis. The matrix (M) protein was expressed in Escherichia coli and purified using a Ni-NTA affinity column chromatography and sucrose density gradient centrifugation. The recombinant M protein with the molecular mass (Mr) of about 43 kDa was detected by anti-NiV serum and anti-myc antibody. About 50% of the M protein was found to be soluble and localized in cytoplasm when the cells were grown at 30 degrees C. Electron microscopic analysis showed that the purified M protein assembled into spherical particles of different sizes with diameters ranging from 20 to 50 nm. The purified M protein showed significant reactivity with the swine sera collected during the NiV outbreak, demonstrating its potential as a diagnostic reagent.

Matched MeSH terms: Swine Diseases/virology; Henipavirus Infections/virology
Fulltext Cloning and expression of highly pathogenic avian influenza virus full-length nonstructural gene in Pichia pastoris

Abubakar MB, Aini I, Omar AR, Hair-Bejo M

J Biomed Biotechnol, 2011;2011:414198.
PMID: 21541235 DOI: 10.1155/2011/414198

Avian influenza (AI) is a highly contagious and rapidly evolving pathogen of major concern to the poultry industry and human health. Rapid and accurate detection of avian influenza virus is a necessary tool for control of outbreaks and surveillance. The AI virus A/Chicken/Malaysia/5858/2004 (H5N1) was used as a template to produce DNA clones of the full-length NS1 genes via reverse transcriptase synthesis of cDNA by PCR amplification of the NS1 region. Products were cloned into pCR2.0 TOPO TA plasmid and subsequently subcloned into pPICZαA vector to construct a recombinant plasmid. Recombinant plasmid designated as pPICZαA-NS1 gene was confirmed by PCR colony screening, restriction enzyme digestion, and nucleotide sequence analysis. The recombinant plasmid was transformed into Pichia pastoris GS115 strain by electroporation, and expressed protein was identified by SDS-PAGE and western blotting. A recombinant protein of approximately ~28 kDa was produced. The expressed protein was able to bind a rabbit polyclonal antibody of nonstructural protein (NS1) avian influenza virus H5N1. The result of the western blotting and solid-phase ELISA assay using H5N1 antibody indicated that the recombinant protein produced retained its antigenicity. This further indicates that Pichia pastoris could be an efficient expression system for a avian influenza virus nonstructural (NS1).

Matched MeSH terms: Chickens/virology*; Influenza in Birds/virology*
Phylogeography of foot-and-mouth disease virus types O and A in Malaysia and surrounding countries

Abdul-Hamid NF, Hussein NM, Wadsworth J, Radford AD, Knowles NJ, King DP

Infect Genet Evol, 2011 Mar;11(2):320-8.
PMID: 21093614 DOI: 10.1016/j.meegid.2010.11.003

Foot-and-mouth disease (FMD) is endemic in the countries of mainland Southeast Asia where it represents a major obstacle to the development of productive animal industries. The aim of this study was to use genetic data to determine the distribution of FMD virus (FMDV) lineages in the Southeast Asia region, and in particular identify possible sources of FMDV causing outbreaks in Malaysia. Complete VP1 sequences, obtained from 214 samples collected between 2000 and 2009, from FMD outbreaks in six Southeast Asian countries, were compared with sequences previously reported. Phylogenetic analysis of these sequences showed that there were two patterns of FMDV distribution in Malaysia. Firstly, for some lineages (O/SEA/Mya98 and serotype A), outbreaks occurred every year in the country and did not appear to persist, suggesting that these incursions were quickly eradicated. Furthermore, for these lineages FMD viruses in Malaysia were closely related to those from neighbouring countries, demonstrating the close epidemiological links between countries in the region. In contrast, for O/ME-SA/PanAsia lineage, viruses were introduced and remained to cause outbreaks in subsequent years. In particular, the recent incursion and maintenance of the PanAsia-2 sublineage into Malaysia appears to be unique and independent from other outbreaks in the region. This study is the first characterisation of FMDV in Malaysia and provides evidence for different epidemiological sources of virus introduction into the country.

Matched MeSH terms: Foot-and-Mouth Disease/virology; Livestock/virology
Fusion of HSP70 gene of Mycobacterium tuberculosis to hemagglutinin (H5) gene of avian influenza virus in DNA vaccine enhances its potency

Rasoli M, Omar AR, Aini I, Jalilian B, Syed Hassan SH, Mohamed M

Acta Virol., 2010;54(1):33-9.
PMID: 20201612

A series of plasmids containing the HSP70 gene of Mycobacterium tuberculosis fused to the hemagglutinin (H5) gene of H5N1 avian influenza virus (AIV) (H5-HSP70 (heat shock protein 70) vaccine) or individual H5 gene (H5 vaccine) or HSP70 gene (HSP70 vaccine) were constructed based on the plasmid pcDNA3.1. Expression of H5 gene in Vero cells in vitro and in chickens in vivo was confirmed following their transfection and immunization with H5 or H5-HSP70 vaccines. Controls consisted of HSP70 vaccine, empty plasmid pcDNA3.1 and co-administered H5 and HSP70 vaccines. H5-HSP70 vaccine produced in chicken higher hemagglutination inhibition (HI) antibody titer than H5 vaccine. However, the increase was not statistically significant. We have demonstrated for the first time that the H5 DNA vaccine with fused HSP70 gene may produce an enhanced induction of humoral immune response to AIV in chickens.

Matched MeSH terms: Influenza in Birds/virology; Poultry Diseases/virology
Fulltext Evaluation of plasma Epstein-Barr virus DNA load as a prognostic marker for nasopharyngeal carcinoma

Tan EL, Looi LM, Sam CK

Singapore Med J, 2006 Sep;47(9):803-7.
PMID: 16924363

Nasopharyngeal carcinoma (NPC) is an important cancer in Malaysia and is one of the major causes of cancer mortality in this country. This study evaluates the diagnostic and prognostic values in the quantitative relationship between the cell-free Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) load and the tumour burden.

Matched MeSH terms: Nasopharyngeal Neoplasms/virology; Epstein-Barr Virus Infections/virology
Cross-reactive T-cell responses to the nonstructural regions of dengue viruses among dengue fever and dengue hemorrhagic fever patients in Malaysia

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/virology; Severe Dengue/virology
Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study

Ooi MH, Wong SC, Podin Y, Akin W, del Sel S, Mohan A, et al.

Clin Infect Dis, 2007 Mar 01;44(5):646-56.
PMID: 17278054

BACKGROUND: Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear.
METHODS: We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates.
RESULTS: Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 [15%] of 168 vs. 30 [28%] of 109; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 [7%] of 168 vs. 29 [27%] of 109; OR, 0.21; 95% CI, 0.10-0.46; P

Matched MeSH terms: Central Nervous System Diseases/virology; Hand, Foot and Mouth Disease/virology

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