ABSTRACT:We valuated specific cellular and humoral immune response of cases of enterovirus 71 (EV71) infection and correlated immune response with clinical outcome. After obtaining informed consent, we enrolled 30 EV71 cases including 7 cases with brainstem encephalitis plus pulmonary edema, 12 cases of CNS (CNS) involvement and 11 uncomplicated cases. We measured antibodies specific to EV71, lymphocyte proliferation response and EV71-stimulated cellular response of Th1/Th2 cytokines and chemokines. The 7 EV71 cases involving brainstem encephalitis plus pulmonary edema had a significantly lower phytohemagglutinin stimulation index than other cases (p ϭ 0.04). After EV71 stimulation of peripheral mononuclear cells, there was a significant increase in cellular Th1 cytokine (␥-interferon) and proinflammatroy cytokines. However, cases with pulmonary edema had significantly lower cellular ␥-interferon reported from the United States, Europe, Australia, Japan, Brazil and Malaysia (1-10), since it was originally characterized from a 1969 California outbreak (1). Before 1998, there were three large outbreaks with dozens of fatal cases occurring in Bulgaria, Hungary, and Malaysia (l975, l978, and 1997, respectively) (3,5,10). The largest and most severe EV71 epidemic to date occurred in Taiwan in 1998 (11-16). A total of 129,106 cases of hand-foot-and-mouth disease and herpangina (HFMD/HA) were reported (15). Severe neurologic complications and/or pulmonary edema were reported in 405 cases, and 78 children died (15).Most EV71 fatalities were cases of fulminant pulmonary edema (15). However, EV71 infection causes very diverse symptoms, ranging from none (about 71%) to fatality (about 0.05%) (17,18). It remains unknown why different hosts of the same EV71 infection have such a range of clinical outcomes (17,18). Perhaps this range is related to virulence or load of the virus, or particular host factors. To date no relationship has been found between EV71 genotypes and clinical outcome (19,20), and EV71 virulence factors have not been clarified. It is possible that host factors, especially host immune response, may be of ultimate importance to clinical outcome.To clarify severe EV71 infection pathogenesis, we investigated factors of cellular versus humoral immune response and correlated this with clinical outcome. SUBJECTS AND METHODS Subjects. After National Taiwan University Hospital Research EthicsCommittee approved this study and informed parental consent was obtained, 30 EV71 cases of different severity were enrolled. EV71 infection was confirmed by positive EV71 isolation and/or positive EV71 specific IgM at the onset of their disease.The CNS involvement was indicated in four types of cases. Those with aseptic meningitis had headache and irritability along with cerebrospinal fluid (CSF) pleocytosis (Ͼ5 leukocytes/L) and without an altered level of consciousness. The second type of cases involved encephalitis had altered level of consciousness plus cerebrospinal fluid (CSF) pleocytosis. Poliomyelitislike syndrome was ...
SummaryIndividual differences in susceptibility to human immunodeficiency virus type 1 (HIV-1) infection have been of interest for decades. We aimed to determine the contribution of large isoform of Mammalian DnaJ (MRJ-L), a HIV-1 Vpr-interacting cellular protein, to this natural variation. Expression of MRJ-L in monocyte-derived macrophages was significantly higher in HIV-infected individuals (n = 31) than their uninfected counterparts (n = 27) (p = 0.009). Fifty male homosexual subjects (20 of them are HIV-1 positive) were further recruited to examine the association between MRJ-L levels and occurrence of HIV infection. Bayesian multiple logistic regression revealed that playing a receptive role and increased levels of MRJ-L in macrophages were two risk factors for HIV-1 infection. A 1% rise in MRJ-L expression was associated with a 1.13 fold (95% CrI 1.06–1.29) increase in odds of contracting HIV-1 infection. Ex vivo experiments revealed that MRJ-L facilitated Vpr-dependent nuclear localization of virus. Infection of macrophage-tropic strain is a critical step in HIV-1 transmission. MRJ-L is a critical factor in this process; hence, subjects with higher macrophage MRJ-L levels are more vulnerable to HIV-1 infection.
Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel SARS-associated coronavirus (SARS-CoV). The clinical characteristics are high fever, rapidly progressive diffuse pneumonitis and respiratory distress. It is highly infectious through intimate contact or direct contact with infectious body fluids. Outbreaks within communities and hospitals have been reported. Development of rapid and reliable diagnostic tools is urgently needed. We developed an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), using whole virus antigen of SARS-CoV. Eighty-six serum samples collected from patients who were hospitalized for other causes were examined to determine the cut-off O.D. value. The cut-off O.D. value was defined as 0.175 by calculating the mean O.D. value of the 86 sera plus 3 standard deviations. To determine the sensitivity and specificity of the ELISA, 56 positive sera and 204 negative sera were tested. The sensitivity was 96.4% and the specificity was 100%. The results suggest that the IgG ELISA using whole virus antigen of SARS-CoV has a high sensitivity and specificity in detecting SARS IgG antibodies. This IgG ELISA is a powerful tool for serodiagnosis of SARS.
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