Displaying publications 1 - 20 of 126 in total

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  1. Experimental cross-infection of sheep and goats with different isolates of contagious ecthyma virus
    Zamri-Saad M, Roshidah I, al-Ajeeli K
    Aust. Vet. J., 1994 Jul;71(7):218-20.
    PMID: 7945102
    Matched MeSH terms: Antigens, Viral/analysis
  2. Fulltext Continuous genotyping for human rotavirus group a
    Zuridah H
    Med J Malaysia, 2012 Oct;67(5):548.
    PMID: 23770884
    Matched MeSH terms: Antigens, Viral
  3. Epitope Identification and Application for Diagnosis of Duck Tembusu Virus Infections in Ducks
    Li C, Liu J, Shaozhou W, Bai X, Zhang Q, Hua R, et al.
    Viruses, 2016 Nov 10;8(11).
    PMID: 27834908
    Duck Tembusu virus (DTMUV) causes substantial egg drop disease. DTMUV was first identified in China and rapidly spread to Malaysia and Thailand. The antigenicity of the DTMUV E protein has not yet been characterized. Here, we investigated antigenic sites on the E protein using the non-neutralizing monoclonal antibodies (mAbs) 1F3 and 1A5. Two minimal epitopes were mapped to (221)LD/NLPW(225) and (87)YAEYI(91) by using phage display and mutagenesis. DTMUV-positive duck sera reacted with the epitopes, thus indicating the importance of the minimal amino acids of the epitopes for antibody-epitope binding. The performance of the dot blotting assay with the corresponding positive sera indicated that YAEYI was DTMUV type-specific, whereas (221)LD/NLPW(225) was a cross-reactive epitope for West Nile virus (WNV), dengue virus (DENV), and Japanese encephalitis virus (JEV) and corresponded to conserved and variable amino acid sequences among these strains. The structure model of the E protein revealed that YAEYI and LD/NLPW were located on domain (D) II, which confirmed that DII might contain a type-specific non-neutralizing epitope. The YAEYI epitope-based antigen demonstrated its diagnostic potential by reacting with high specificity to serum samples obtained from DTMUV-infected ducks. Based on these observations, a YAEYI-based serological test could be used for DTMUV surveillance and could differentiate DTMUV infections from JEV or WNV infections. These findings provide new insights into the organization of epitopes on flavivirus E proteins that might be valuable for the development of epitope-based serological diagnostic tests for DTMUV.
    Matched MeSH terms: Antigens, Viral/immunology
  4. Identification of epitopes in the nucleocapsid protein of Nipah virus using a linear phage-displayed random peptide library
    Eshaghi M, Tan WS, Yusoff K
    J Med Virol, 2005 Jan;75(1):147-52.
    PMID: 15543570
    A random peptide library of heptamers displayed on the surface of M13 bacteriophage was used to identify specific epitopes of antibodies in pooled sera of swine naturally infected by Nipah virus. The selected heptapeptides were aligned with protein sequences of Nipah virus and several putative epitopes were identified within the nucleocapsid protein. A total of 41 of 60 (68%) selected phage clones had inserts resembling a region with the sequence SNRTQGE, located at the C-terminal end (amino acids 503-509) of the nucleocapsid protein. The binding of antibodies in the swine and human antisera to the phage clone was inhibited by a synthetic peptide corresponding to this region. Epitopes identified by phage display are consistent with the predicted antigenic sites for the Nipah virus nucleocapsid protein. The selected phage clone used as a coating antigen discriminated swine and human Nipah virus sera-positive from sera-negative samples exhibiting characteristics, which might be attractive for diagnostic tests.
    Matched MeSH terms: Antigens, Viral
  5. Solubility, immunogenicity and physical properties of the nucleocapsid protein of Nipah virus produced in Escherichia coli
    Tan WS, Ong ST, Eshaghi M, Foo SS, Yusoff K
    J Med Virol, 2004 May;73(1):105-12.
    PMID: 15042656
    The nucleocapsid (N) protein of Nipah virus (NiV) can be produced in three Escherichia coli strains [TOP10, BL21(DE3) and SG935] under the control of trc promoter. However, most of the product existed in the form of insoluble inclusion bodies. There was no improvement in the solubility of the product when this protein was placed under the control of T7 promoter. However, the solubility of the N protein was significantly improved by lowering the growth temperature of E. coli BL21(DE3) cell cultures. Solubility analysis of N- and C-terminally deleted mutants revealed that the full-length N protein has the highest solubility. The soluble N protein could be purified efficiently by sucrose gradient centrifugation and nickel affinity chromatography. Electron microscopic analysis of the purified product revealed that the N protein assembled into herringbone-like particles of different lengths. The C-terminal end of the N protein contains the major antigenic region when probed with antisera from humans and pigs infected naturally.
    Matched MeSH terms: Antigens, Viral
  6. Nipah virus glycoprotein: production in baculovirus and application in diagnosis
    Eshaghi M, Tan WS, Mohidin TB, Yusoff K
    Virus Res, 2004 Nov;106(1):71-6.
    PMID: 15522449
    A method for serological diagnosis of Nipah virus (NiV) is described. DNA encoding truncated G protein of NiV was cloned into the pFastBac HT vector, and the fusion protein to His-tag was expressed in insect cells by recombinant baculovirus. The resulting His-G recombinant fusion protein was purified by affinity chromatography and used as the coating antigen for serological testing by indirect enzyme-linked immunosorbant assay (ELISA). When tested against a panel of swine serum samples, the recombinant G protein-based ELISA successfully discriminated all 40 samples previously determined to be serum neutralizing test (SNT) positive from 11 SNT negatives samples. The data show that the recombinant G protein exhibits the antigenic epitopes and conformation necessary for specific antigen-antibody recognition. The main advantage of the recombinant G protein-based NiV ELISA compared to an ELISA using whole virus antigen is the use of a single antigenic protein instead of inactivated whole virus which is required to be prepared under high risk and cost. This test is suitable for routine diagnosis of NiV and also for epidemiological surveys as it allows highly reliable testing of a large number of sera rapidly.
    Matched MeSH terms: Antigens, Viral/immunology*; Antigens, Viral/chemistry
  7. Fulltext Surface display of respiratory syncytial virus glycoproteins in Lactococcus lactis NZ9000
    Lim SH, Jahanshiri F, Rahim RA, Sekawi Z, Yusoff K
    Lett Appl Microbiol, 2010 Dec;51(6):658-64.
    PMID: 20973806 DOI: 10.1111/j.1472-765X.2010.02950.x
    A system for displaying heterologous respiratory syncytial virus (RSV) glycoproteins on the surface of Lactococcus lactis NZ9000 was developed.
    Matched MeSH terms: Antigens, Viral/metabolism
  8. Fulltext Rapid testing requires clinical evaluation for accurate diagnosis of dengue disease: A passive surveillance study in Southern Malaysia
    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: Antigens, Viral/blood
  9. Isolation, identification and characterization of chicken anaemia virus in Malaysia
    Chowdhury SM, Omar AR, Aini I, Hair-Bejo M, Jamaluddin AA, Kono Y, et al.
    J. Biochem. Mol. Biol. Biophys., 2002 Aug;6(4):249-55.
    PMID: 12186740
    A study was conducted to isolate and identify chicken anaemia virus (CAV) from field samples of clinically infected broiler chickens in Malaysia. A total of 125 samples were collected from chickens aged 2-6 weeks with clinically depressed and retarded growth, of which five samples were found positive to CAV directly by polymerase chain reaction (PCR). Later, five isolates of CAV from the respective five PCR positive samples were isolated in MDCC-MSB1 cells at passage 4 based on cytopathic effects, PCR and indirect immunofluorescent antibody test. The isolates were identified as BL-1, BL-2, BL-3, BL-4 and BL-5. These CAV isolates were found to resist treatment with chloroform and heat at 37 degrees C for 2 h, 56 degrees C for 30 min and 70 degrees C for 5 min. One of the isolates, BL-5 produced significant reduction (p < 0.001) of hematocrit values (9-19%), pale bone marrow, thymus atrophy and haemorrhages in skin/muscle when inoculated into 1-day old SPF chickens. Restriction enzyme digestion of 926 bp genomic fragments of all the isolates including Cux-1 isolate with HindIII exhibited a similar pattern of bands in 2% agarose gel. The present findings confirmed the presence of CAV in Malaysia.
    Matched MeSH terms: Antigens, Viral/metabolism
  10. Development of a slide latex agglutination test for rotavirus antigen detection
    Yap KL
    Malays J Pathol, 1994 Jun;16(1):49-56.
    PMID: 16329576
    The aim of this study was to optimize the conditions for the passive adsorption of polyclonal antibody onto plain surface polystyrene latex particles and its performance in a slide latex agglutination test for rotavirus antigen detection. Cleaning of latex particles by washing through repetitive centrifuging, decanting and resuspending in distilled water was adequate in removing surfactants from the particles' surfaces to enable coating. A study of antibody concentration, incubation temperature and buffer pH revealed that optimum coating was achieved with a 3-fold excess of antibody to the calculated total particle surface capacity for the antibody in a glycine-saline buffer of pH 9.2 at 40 degrees C for 4 hours. The ionic strength and pH of the latex suspending buffer and the sample buffer were critical factors determining the sensitivity of the test and the appearance of non-specific agglutination. Ultrasonication, addition of glycerol and Tween 20, either individually or in combination, were able to suppress non-specific agglutination in some batches of latex reagents. Polyethylene glycol 6000 enhanced the quality of agglutination as well as reduced the time of its appearance, especially in reagents that produced poor agglutination.
    Matched MeSH terms: Antigens, Viral/immunology
  11. A molecular epidemiological study targeting the glycoprotein gene of rabies virus isolates from China
    Meng SL, Yan JX, Xu GL, Nadin-Davis SA, Ming PG, Liu SY, et al.
    Virus Res, 2007 Mar;124(1-2):125-38.
    PMID: 17129631
    A group of 31 rabies viruses (RABVs), recovered primarily from dogs, one deer and one human case, were collected from various areas in China between 1989 and 2006. Complete G gene sequences determined for these isolates indicated identities of nucleotide and amino acid sequences of >or=87% and 93.8%, respectively. Phylogenetic analysis of these and some additional Chinese isolates clearly supported the placement of all Chinese viruses in Lyssavirus genotype 1 and divided all Chinese isolates between four distinct groups (I-IV). Several variants identified within the most commonly encountered group I were distributed according to their geographical origins. A comparison of representative Chinese viruses with other isolates retrieved world-wide indicated a close evolutionary relationship between China group I and II viruses and those of Indonesia while China group III viruses formed an outlying branch to variants from Malaysia and Thailand. China group IV viruses were closely related to several vaccine strains. The predicted glycoprotein sequences of these RABVs variants are presented and discussed with respect to the utility of the anti-rabies biologicals currently employed in China.
    Matched MeSH terms: Antigens, Viral/genetics*; Antigens, Viral/chemistry
  12. Anti-tumour promoter activity in Malaysian ginger rhizobia used in traditional medicine
    Vimala S, Norhanom AW, Yadav M
    Br. J. Cancer, 1999 Apr;80(1-2):110-6.
    PMID: 10389986
    Zingiberaceae rhizomes commonly used in the Malaysian traditional medicine were screened for anti-tumour promoter activity using the short-term assay of inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) in Raji cells. The inhibition of TPA-induced EBV-EA was detected using the indirect immunofluorescence assay (IFA) and Western blot technique. The indirect IFA detected the expression/inhibition of EBV-EA-D (diffused EA antigen), whereas the Western blot technique detected the expression/inhibition of both EBV-EA-D and EA-R (restricted EA antigen). Seven rhizomes were found to possess inhibitory activity towards EBV activation, induced by TPA; they are: Curcuma domestica, C. xanthorrhiza, Kaempferia galanga, Zingiber cassumunar, Z. officinale, Z. officinale (red variety), and Z. zerumbet. A cytotoxicity assay was carried out to determine the toxicity of the Zingiberaceae rhizome extracts. The rhizome extracts that exhibited EBV activation inhibitory activity had no cytotoxicity effect in Raji cells. Therefore, the present study shows that several Zingiberaceae species used in Malaysian traditional medicine contain naturally occurring non-toxic compounds that inhibit the EBV activation, which, if further investigated, could contribute in the development of cancer prevention methods at the tumour-promoting stage.
    Matched MeSH terms: Antigens, Viral*
  13. Inhibition of tumour promotion by various palm-oil tocotrienols
    Goh SH, Hew NF, Norhanom AW, Yadav M
    Int J Cancer, 1994 May 15;57(4):529-31.
    PMID: 8181855
    Inhibition of tumour promotion by various vitamin E compounds (tocopherols and tocotrienols) and some of their dimers was examined by an in vitro assay utilizing the activation of Epstein-Barr virus (EBV) early antigen (EA) expression in EBV-genome-carrying human lymphoblastoid cells. The results reveal that gamma- and delta-tocotrienols derived from palm oil exhibit a strong activity against tumour promotion by inhibiting EBV EA expression in Raji cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). However, alpha- and gamma-tocopherols and dimers of gamma-tocotrienol or gamma-tocopherol lack this activity.
    Matched MeSH terms: Antigens, Viral/physiology
  14. Tumour promoter activity in Malaysian Euphorbiaceae
    Norhanom AW, Yadav M
    Br. J. Cancer, 1995 Apr;71(4):776-9.
    PMID: 7710943
    Herbal medication has been practised by the rural Malaysian Malays for a long time. However, the long-term side-effects have never been studied. In the present study, 48 species of Euphorbiaceae were screened for tumour-promoter activity by means of an in vitro assay using a human lymphoblastoid cell line harbouring the Epstein-Barr virus (EBV) genome. Twenty-seven per cent (13 out of 48) of the species tested were found to be positive, and in four species, namely Breynia coronata Hk.f, Codiaeum variegatum (L) Bl, Euphorbia atoto and Exocoecaria agallocha, EBV-inducing activity was observed when the plant extracts were tested at low concentrations of between 0.2 and 1.2 micrograms ml-1 in cell culture. This observation warrants attention from the regular users of these plants because regular use of plants with tumour-promoting activity could well be an aetiological factor for the promotion of tumours among rural Malaysian Malays.
    Matched MeSH terms: Antigens, Viral/biosynthesis
  15. Fulltext Pathological findings in a mouse model of Japanese encephalitis infected via the footpad
    Fu, Tzeh Long, Ong, Kien Chai, Wong, Kum Thong
    Neurology Asia, 2015;20(4):349-354.
    MyJurnal
    We have developed and characterised a mouse model of Japanese encephalitis virus (JEV) infection via
    footpad inoculation in order to better mimic viral transmission by mosquito bites. Two-week-old and
    5-week-old mice consistently developed signs of infection such as ruffled fur, weight loss, hunchback
    posture, tremors, mask-like facies and occasionally, hindlimb paralysis at 4 days post infection (dpi)
    and 11-13 dpi, respectively. Most of the animals died within 24 to 48 hours following the onset of signs
    of infection, with mortalities of 100% and 33.3% in 2-week-old and 5-week-old mice, respectively.
    Mild meningitis and variable parenchymal inflammation with formation of microglial nodules, focal
    necrosis and neuronophagia, and perivascular cuffing by inflammatory cells were observed in the
    caudate nucleus, putamen, thalamus, cerebral cortex, brainstem, and spinal cord. Viral antigens/RNA
    were demonstrated by immunohistochemisty and in situ hybridization, respectively, in most of these
    areas as well as in the hippocampus and cerebellum, albeit more focally. The pathological findings in
    this mouse model were generally similar to human Japanese encephalitis (JE) and other established JE
    models but perhaps, compared to other JEV mouse models, it demonstrates lethal encephalitic infection
    more consistently. We believe that our mouse model should be useful to study the pathogenesis of JE,
    and for testing anti-viral drugs and vaccines
    Matched MeSH terms: Antigens, Viral
  16. Fulltext Pathological findings in a mouse model for Coxsackievirus A16 infection
    Hooi, Yuan Teng, Ong, Kien Chai, Perera, David, Wong, Kum Thong
    Neurology Asia, 2015;20(4):343-347.
    MyJurnal
    Coxsackievirus A16 (CV-A16) is the leading cause of hand-foot-mouth disease (HFMD), which usually
    presents as mild and self-limiting symptoms in young children. Rarely, CV-A16 has been reported
    to cause severe and fatal neurological complications but little is known about these complications.
    In the present study, 1-day and 7-day old mouse models of CV-A16 were developed using a clinical
    strain via subcutaneous inoculation. All infected mice exhibited clinical signs of infection, including
    reduced mobility, limb weakness and paralysis between 3 to 6 days post-infection. Pathologically,
    the main organs involved were the central nervous system (CNS), skeletal muscles and brown fat. In
    the CNS, viral antigens as demonstrated by immunohistochemistry, were localized mainly to neurons
    in the brain stem and spinal cord, suggesting that CV-A16 is neurotropic although inflammation is
    very mild. The skeletal muscles showed necrosis and myositis due to viral infection as evidenced by
    the dense viral antigens. Focal viral antigens were also detected in the brown fat. These preliminary
    pathological findings indicate that our mouse models can be further developed to be useful models
    for pathogenesis studies, and vaccine and anti-viral drug evaluation.
    Matched MeSH terms: Antigens, Viral
  17. Fulltext Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis
    Ong KC, Badmanathan M, Devi S, Leong KL, Cardosa MJ, Wong KT
    J. Neuropathol. Exp. Neurol., 2008 Jun;67(6):532-42.
    PMID: 18520772 DOI: 10.1097/NEN.0b013e31817713e7
    We describe a model of Enterovirus 71 encephalomyelitis in 2-week-old mice that shares many features with the human central nervous system (CNS) disease. Mice were infected via oral and parenteral routes with a murine-adapted virus strain originally from a fatal human case. The mice succumbed to infection after 2 to 5 days. Vacuolated and normal-appearing CNS neurons showed viral RNA and antigens and virions by in situ hybridization, immunohistochemistry, and electron microscopy; inflammation was minimal. The most numerous infected neurons were in anterior horns, motor trigeminal nuclei, and brainstem reticular formation; fewer neurons in the red nucleus, lateral cerebellar nucleus, other cranial nerve nuclei, motor cortex, hypothalamus, and thalamus were infected. Other CNS regions, dorsal root, and autonomic ganglia were spared. Intramuscular-inoculated mice killed 24 to 36 hours postinfection had viral RNA and antigens in ipsilateral lumbar anterior horn cells and adjacent axons. Upper cord motor neurons, brainstem, and contralateral motor cortex neurons were infected from 48-72 hours. Viral RNA and antigens were abundant in skeletal muscle and adjacent tissues but not in other organs. The distinct, stereotypic viral distribution in this model suggests that the virus enters the CNS via peripheral motor nerves after skeletal muscle infection, and spread within the CNS involves motor and other neural pathways. This model may be useful for further studies on pathogenesis and for testing therapies.
    Matched MeSH terms: Antigens, Viral/analysis
  18. Neuronal transcriptomic responses to Japanese encephalitis virus infection with a special focus on chemokine CXCL11 and pattern recognition receptors RIG-1 and MDA5
    Yu SP, Ong KC, Perera D, Wong KT
    Virology, 2019 01 15;527:107-115.
    PMID: 30481615 DOI: 10.1016/j.virol.2018.10.015
    Japanese encephalitis virus (JEV) causes central nervous system neuronal injury and inflammation. A clear understanding of neuronal responses to JEV infection remains elusive. Using the Affymetrix array to investigate the transcriptome of infected SK-N-MC cells, 1316 and 2737 dysregulated genes (≥ 2/-2 fold change, P 
    Matched MeSH terms: Antigens, Viral/metabolism
  19. Localization of dengue virus in naturally infected human tissues, by immunohistochemistry and in situ hybridization
    Jessie K, Fong MY, Devi S, Lam SK, Wong KT
    J Infect Dis, 2004 Apr 15;189(8):1411-8.
    PMID: 15073678
    Dengue viral antigens have been demonstrated in several types of naturally infected human tissues, but little is known of whether these same tissues have detectable viral RNA. We studied tissue specimens from patients with serologically or virologically confirmed dengue infections by immunohistochemistry (IHC) and in situ hybridization (ISH), to localize viral antigen and RNA, respectively. IHC was performed on specimens obtained from 5 autopsies and 24 biopsies and on 20 blood-clot samples. For ISH, antisense riboprobes to the dengue E gene were applied to tissue specimens in which IHC was positive. Viral antigens were demonstrated in Kupffer and sinusoidal endothelial cells of the liver; macrophages, multinucleated cells, and reactive lymphoid cells in the spleen; macrophages and vascular endothelium in the lung; kidney tubules; and monocytes and lymphocytes in blood-clot samples. Positive-strand viral RNA was detected in the same IHC-positive cells found in the spleen and blood-clot samples. The strong, positive ISH signal in these cells indicated a high copy number of viral RNA, suggesting replication.
    Matched MeSH terms: Antigens, Viral/analysis*
  20. A novel orally infected hamster model for Coxsackievirus A16 hand-foot-and-mouth disease and encephalomyelitis
    Hooi YT, Ong KC, Tan SH, Perera D, Wong KT
    Lab Invest, 2020 Sep;100(9):1262-1275.
    PMID: 32601355 DOI: 10.1038/s41374-020-0456-x
    Coxsackievirus A16 (CV-A16) is one of the major causes of mild and self-limiting hand-foot-and-mouth disease (HFMD) in young children, which may occasionally leads to serious neurological complications. In this study, we had developed a novel, consistent, orally infected CV-A16 HFMD hamster model with encephalomyelitis. Four groups of 7-day-old hamsters in a kinetic study were orally infected with mouse-adapted CV-A16 strains and sacrificed at 1-4 days post infection (dpi), respectively. Tissues were studied by light microscopy, immunohistochemistry to detect viral antigens, in situ hybridization to detect viral RNA, and by viral titration. In a separate transmission experiment, orally infected index hamsters were housed together with contact hamsters to investigate oral and fecal viral shedding by virus culture and reverse transcription polymerase chain reaction (RT-PCR). At severe infection/death endpoints, index and contact hamster infection were also histopathologically analyzed. In the kinetic study, infected hamsters developed signs of infection at 4 dpi. Viral antigens/RNA were localized to brainstem (medulla/pons; reticular formation and motor trigeminal nucleus) and spinal cord anterior horn neurons, oral squamous epithelia and epidermis from 3 to 4 dpi. Salivary and lacrimal glands, myocardium, brown adipose tissue, intestinal smooth muscle, and skeletal muscle infection was also demonstrated. Viremia at 1 dpi and increasing viral titers in various tissues were observed from 2 dpi. In the transmission study, all contact hamsters developed disease 3-5 days later than index hamsters, but demonstrated similar histopathological findings at endpoint. Viral culture and RT-PCR positive oral washes and feces confirmed viral shedding. Our hamster model, orally infected by the natural route for human infection, confirmed CV-A16 neurotropism and demonstrated squamous epitheliotropism reminiscent of HFMD, attributes not found in other animal models. It should be useful to investigate neuropathogenesis, model person-to-person transmission, and for testing antiviral drugs and vaccines.
    Matched MeSH terms: Antigens, Viral/metabolism
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