SARS-CoV Regulates Immune Function-Related Gene Expressions in Human Monocytic Cells

Background: Severe Acute Respiratory Syndrome (SARS) is characterized by acute respiratory distress (ARDS) and pulmonary fibrosis, and the monocyte/macrophage is the key player in the pathogenesis of SARS.
 
Methods: In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV) infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after infection and the gene expression was profiled by oligonucleotide-based microarray. 

Results: Analysis of immune-related gene expression profiles showed that 24 h after SARS-CoV infection, (i) IFN-alpha/beta-inducible and cathepsin/proteosome genes were down-regulated; (ii) the hypoxia/hyperoxia-related genes were up-regulated; and (iii) the TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, the lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. 

Conclusion: These results elucidate that monocyte/macrophage dysfunction and dysregulation of fibrosis-related genes are two important pathogenic events of SARS. 
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An Outbreak of Coxsackievirus A16 Infection: Comparison With Other Enteroviruses in a Preschool in Taipei

Background/PurposeThe transmission rate of enteroviruses in young children remains unclear. Therefore, we carried out active surveillance in preschool children to investigate the transmission rate and clinical manifestation of enteroviruses.MethodsFrom September 2006 to December 2008, we monitored infectious diseases in children 2(–3 years of age) in a preschool in Taipei. If any child had a febrile illness or symptoms/signs of enteroviral infection [e.g. herpangina or hand-foot-and-mouth disease (HFMD)], we performed viral isolation and enterovirus polymerase chain reaction. VP1 sequencing was performed to define their serotypes. We also collected clinical data and analyzed transmission rates.ResultsThere were eight episodes of enterovirus infection during the study period. The serotypes included coxsackievirus A4 (CA4), CA2 and CA16. The transmission rates of CA4 and CA2 among children in same class were 26% and 35%, respectively. Between November 28 and December 12, 2008, 13/21 (61.9%) children contracted herpangina and/or HFMD. The average age was 2.82 (range, 2.43–3.39) years. CA16 was detected in 10/13 (76.9%) of the throat swabs by polymerase chain reaction VP1 genotyping. Compared with previous CA2 and CA4 outbreaks, CA16 had a significantly higher transmission rate (p = 0.035) and resulted in more cases of HFMD (p < 0.001). The transmission duration of coxsackie A viruses within the same class ranged from 12 to 40 days.ConclusionCompared with CA2 and CA4, CA16 infections resulted in more cases of HFMD and had significantly higher transmission rates in preschoolers

Epidemic Pleurodynia Caused by Coxsackievirus B3 at a Medical Center in Northern Taiwan

Epidemic pleurodynia is seldom reported in Southeast Asia and there has been no report from Taiwan. We conducted a retrospective chart review of children = 18 years of age in the National Taiwan University Hospital from January 1 to December 31, 2005. Epidemic pleurodynia was defined as an acute illness characterized by sharp localized pain over the chest or upper abdomen. Patients with known heart diseases or pulmonary consolidations were excluded. In total, 28 patients met the case definition of epidemic pleurodynia. Coxsackievirus B3 (CB3) was isolated in 15 (60%) of the 25 throat swab specimens. Four (14%) of the 28 patients presented chest wall tenderness and only one (6%) of the 18 patients tested had an elevated creatinine kinase level. Twenty-one (75%) of the 28 patients described pleuritic chest pains and 10 (45%) of the 22 chest radiographies exhibited pulmonary infiltrates or pleural effusions. Six patients were observed with tonsillar exudates and one was confirmed to have a CB3 urinary tract infection. The clinical features and radiological findings suggest that CB3-associated epidemic pleurodynia might be a disease of the pleura and occasionally spreads to nearby tissues, resulting in chest wall myositis, pulmonary infiltrates and myopericarditis

Seroprevalence of enterovirus 71 and no evidence of crossprotection of enterovirus 71 antibody against the other enteroviruses in kindergarten children in Taipei city

Background/PurposeEnterovirus 71 (EV71) infection may cause severe neurological and cardiopulmonary complications, especially in preschool children. This study is to investigate the seroprevalence and seroconversion of EV71, and the crossprotection of EV71 antibody against other enteroviruses among kindergarteners.MethodsOverall 228 children in a public kindergarten were enrolled during two academic years, 2006 and 2007, in Taipei, Taiwan and we measured their EV71 neutralizing antibody. When the participants had herpangina; hand, foot and mouth disease (HFMD); febrile illness or respiratory symptoms, throat swabs were sampled and processed for viral culture and enterovirus real-time reverse transcriptase polymerase chain reaction (RT-PCR). Questionnaires, completed by the participants’ guardians, surveyed the history of allergy and annual incidence of symptoms related to enterovirus infection.ResultsSeropositive rates of EV71 were 20% (32/163) in 2006 and 6% (4/65) in 2007. The rate of EV71 seropositivity increased with age (p < 0.01) in 2006 but it did not differ between genders (p = 0.14). No seroconversion was observed from 2006 to 2007. Herpangina occurred in 64% of children with EV71 seropositivity and 48% of those without EV71 antibodies (p = 0.12). Non-71 enterovirus infection, confirmed by viral study, occurred in 53% (19/36) of the EV71-seropositive children and in 53% (102/192) of EV71-seronegative children (p = 0.89). No participants had EV71 infection during the study period.ConclusionEV71 did not frequently circulate in Taipei City from September 2006 to June 2008. Presence of EV71 neutralizing antibody was not associated with lower incidence of enterovirus infection caused by non-71 serotypes

Viral load and clinical features in children infected with seasonal influenza B in 2006/2007

Background/PurposeIn influenza B infection, viral load is believed to be related to the severity of clinical illness. The correlation between viral load and symptoms is not known. We conducted a study to assess the relationship between virus load and clinical features in children infected with influenza B, in the hope that clinical features could be used as surrogate markers of viral load to guide treatment.MethodsBetween December 2006 and February 2007, 228 patients with fever and respiratory symptoms were prospectively enrolled in our tertiary hospital-based study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine viral load.ResultsReal-time RT-PCR was positive for influenza B in 76 patients. Using virus culture as the gold standard, the sensitivity and specificity were 95% and 87%, respectively. Influenza culture positive rate significantly correlated with viral load (p = 0.03). The median copy number of influenza B virus in the 76 RT-PCR positive patients was 9735 copies/ml (range 4.8×101–2.0×106 copies/ml). Samples obtained later in the clinical course tended to have lower viral load (p = 0.7), while patient age (p = 0.72) and fever duration (p = 0.96) positively related to viral load. In patients >3 years of age, myalgia was related to statistically lower viral loads (14300 vs. 1180; p = 0.025). Patients with chills tended to have higher viral loads (72450 vs. 7640; p = 0.1). Patients with abdominal pain tended to have lower viral loads (1998 vs. 12550; p = 0.06).ConclusionCulture rate positively correlated with viral load. Patients with myalgia had a lower viral load

Evaluation of the Kinetic Change of the Immunogenicity of Dengue-2 DNA Vaccine in Mice Administered by Different Administration Routes

A plasmid DNA vaccine is able to induce both humoral and cellular immune responses; however, the kinetic change of the Th1/Th2 response, antibody avidity, cytokine secretion, and neutralization activity after different priming and boosting strategies have not been evaluated. A plasmid DNA, designated pCBD2 and previously shown to efficiently induce an immune response very similar to that by a wild type virus, was evaluated kinetically in this study. Our results suggest that a DNA vaccine delivered by the gene gun (gg) route produced higher and longer DENV-2-specific anti-body titers than those induced through the intramuscular (im) route. Although the gg group induced a Th2 response and im delivery induced a Th1 response, priming by gg delivery, followed by a boosting by im delivery, did not shift the immune response from a Th2 to Th1 response. Furthermore, the antibody avidity (AI) measured by ELISA demon-strated a gradual increase of AI from low (AI range from 6.8% - 9.6%) on day 42 to high (AI value > 30) on day 119 in all but the gene-gun immunization group, in which an AI value of 23 was observed. Although there was lower avidity in the gg group, the mice sera from all three groups of mice demonstrated significant neutralization activity. This is the first report about the kinetics of immunogenicity of a DNA vaccine through different administration strategies, which suggests that gene gun delivery of a DNA vaccine can induce an immune response containing both neutralizing and nonneutralizing antibodies at high titers important for neutralization

Microbiologic Characteristics, Serologic Responses, and Clinical Manifestations in Severe Acute Respiratory Syndrome, Taiwan1

The genome of one Taiwanese severe acute respiratory syndrome-associated coronavirus (SARS-CoV) strain (TW1) was 29,729 nt in length. Viral RNA may persist for some time in patients who seroconvert, and some patients may lack an antibody response (immunoglobulin G) to SARS-CoV >21 days after illness onset. An upsurge of antibody response was associated with the aggravation of respiratory failure

SARS Exposure and Emergency Department Workers

Of 193 emergency department workers exposed to severe acute respiratory syndrome (SARS), 9 (4.7%) were infected. Pneumonia developed in six workers, and assays showed anti-SARS immunoglobulin (Ig) M and IgG. The other three workers were IgM-positive and had lower IgG titers; in two, mild illness developed, and one remained asymptomatic