Serological response to a third dose of SARS-CoV-2 vaccine according to previous infection history.

The IgG antibody titer against SARS-CoV-2 receptor binding protein (RBD) after mRNA vaccine were compared between those with and without previous infection (PI) for up to 48 weeks. Though sustained higher IgG-RBD were observed in the PI group after two doses of vaccines, both groups benefited from the booster shots of the third vaccine. This data supports the necessity of the booster shots to those with PI.

Paradoxical expression of IL-28B mRNA in peripheral blood in human T-cell leukemia virus type-1 mono-infection and co-infection with hepatitis C virus.

BACKGROUND: Human T-cell leukemia virus type-1 (HTLV-1) carriers co-infected with and hepatitis C virus (HCV) have been known to be at higher risk of their related diseases than mono-infected individuals. The recent studies clarified that IL-28B polymorphism rs8099917 is associated with not only the HCV therapeutic response by IFN, but also innate immunity and antiviral activity. The aim of our research was to clarify study whether IL-28B gene polymorphism (rs8099917) is associated with HTLV-1/HCV co-infection. RESULTS: The genotyping and viral-serological analysis for 340 individuals showed that IL-28B genotype distribution of rs8099917 SNP did not differ significantly by respective viral infection status. However, the IL-28B mRNA expression level was 3.8 fold higher in HTLV-1 mono-infection than HTLV-1/HCV co-infection. The high expression level was associated with TT (OR, 6.25), whiles the low expression was associated with co-infection of the two viruses (OR, 9.5). However, there was no association between down-regulation and ATL development (OR, 0.8). CONCLUSION: HTLV-1 mono-infection up-regulates the expression of IL-28B transcripts in genotype-dependent manner, whiles HTLV-1/HCV co-infection down-regulates regardless of ATL development.

Human T-cell leukemia virus type 1 infection worsens prognosis of hepatitis C virus-related living donor liver transplantation.

Severe and life-threatening donor-transmitted human T-cell leukemia virus type 1 (HTLV-1) infections after solid organ transplantation have been reported. However, in HTLV-1-infected recipients, graft and patient survival were not fully evaluated. A total of 140 patients underwent living donor liver transplantation (LDLT). Of these, 47 of 126 adult recipients showed indications of hepatitis C virus (HCV)-related liver disease. The HTLV-1 prevalence rate was 10 of 140 recipients (7.14%) and three of 140 donors (0.02%). In HCV-related LDLT, graft and patient survival was worsened by HTLV-1 infection in recipients (seven cases). The 1-, 3-, and 5-year survival rates in the HCV/HTLV-1-co-infected group were 67%, 32%, and 15%, respectively, and the corresponding rates in the HCV-mono-infected group were 80%, 67%, and 67%, respectively. Only the 5-year survival rates were statistically significant (P=0.04, log-rank method). HTLV-1 infection in recipients is also an important factor in predicting survival in HTLV-1 endemic areas.

Public Interest and Accessibility of Telehealth in Japan: Retrospective Analysis Using Google Trends and National Surveillance.

BACKGROUND: Recently, the use of telehealth for patient treatment under the COVID-19 pandemic has gained interest around the world. As a result, many infodemiology and infoveillance studies using web-based sources such as Google Trends were reported, focusing on the first wave of the COVID-19 pandemic. Although public interest in telehealth has increased in many countries during this time, the long-term interest has remained unknown among people living in Japan. Moreover, various mobile telehealth apps have become available for remote areas in the COVID-19 era, but the accessibility of these apps in epidemic versus nonepidemic regions is unknown. OBJECTIVE: We aimed to investigate the public interest in telehealth during the first pandemic wave and after the wave in the first part of this study, and the accessibility of medical institutions using telehealth in the epidemic and nonepidemic regions, in the second part. METHODS: We examined and compared the first wave and after the wave with regards to severe cases, number of deaths, relative search volume (RSV) of telehealth and COVID-19, and the correlation between RSV and COVID-19 cases, using open sources such as Google Trends and the Japanese Ministry of Health, Labour and Welfare (JMHLW) data. The weekly mean and the week-over-week change rates of RSV and COVID-19 cases were used to examine the correlation coefficients. In the second part, the prevalence of COVID-19 cases, severe cases, number of deaths, and the telehealth accessibility rate were compared between epidemic regions and nonepidemic regions, using the JMHLW data. We also examined the regional correlation between telehealth accessibility and the prevalence of COVID-19 cases. RESULTS: Among the 83 weeks with 5 pandemic waves, the overall mean for the RSV of telehealth and COVID-19 was 11.3 (95% CI 8.0-14.6) and 30.7 (95% CI 27.2-34.2), respectively. The proportion of severe cases (26.54% vs 18.16%; P<.001), deaths (5.33% vs 0.99%; P<.001), RSV of telehealth (mean 33.1, 95% CI 16.2-50.0 vs mean 7.3, 95% CI 6.7-8.0; P<.001), and RSV of COVID-19 (mean 52.1, 95% CI 38.3-65.9 vs mean 26.3, 95% CI 24.4-29.2; P<.001) was significantly higher in the first wave compared to after the wave. In the correlation analysis, the public interest in telehealth was 0.899 in the first wave and -0.300 overall. In Japan, the accessibility of telehealth using mobile apps was significantly higher in epidemic regions compared to nonepidemic regions in both hospitals (3.8% vs 2.0%; P=.004) and general clinics (5.2% vs 3.1%; P<.001). In the regional correlation analysis, telehealth accessibility using mobile apps was 0.497 in hospitals and 0.629 in general clinics. CONCLUSIONS: Although there was no long-term correlation between the public interest in telehealth and COVID-19, there was a regional correlation between mobile telehealth app accessibility in Japan, especially for general clinics. We also revealed that epidemic regions had higher mobile telehealth app accessibility. Further studies about the actual use of telehealth and its effect after the COVID-19 pandemic are necessary.

Characteristic expression of HTLV-1 basic zipper factor (HBZ) transcripts in HTLV-1 provirus-positive cells.

BACKGROUND: HTLV-1 causes adult T-cell leukemia (ATL). Although there have been many studies on the oncogenesis of the viral protein Tax, the precise oncogenic mechanism remains to be elucidated. Recently, a new viral factor, HTLV-1 basic Zip factor (HBZ), encoded from the minus strand mRNA was discovered and the current models of Tax-centered ATL cell pathogenesis are in conflict with this discovery. HBZs consisting of non-spliced and spliced isoforms (HBZ-SI) are thought to be implicated in viral replication and T-cell proliferation but there is little evidence on the HBZ expression profile on a large scale. RESULTS: To investigate the role of HBZ-SI in HTLV-1 provirus-positive cells, the HBZ-SI and Tax mRNA loads in samples with a mixture of infected and non-infected cells were measured and then adjusted by dividing by the HTLV-I proviral load. We show here that the HBZ-SI mRNA level is 4-fold higher than non-spliced HBZ and is expressed by almost all cells harboring HTLV-1 provirus with variable intensity. The proviral-adjusted HBZ-SI and Tax quantification revealed a characteristic imbalanced expression feature of high HBZ and low Tax expression levels in primary ATL cells or high HBZ and very high Tax levels in HTLV-1-related cell lines (cell lines) compared with a standard expression profile of low HBZ and low Tax in infected cells. Interestingly, according to the mutual Tax and HBZ expression status, HTLV-1-related cell lines were subcategorized into two groups, an ATL cell type with high HBZ and low Tax levels and another type with high Tax and either high or low HBZ, which was closely related to its cell origin. CONCLUSION: This is the first comprehensive study to evaluate the mutual expression profile of HBZ and Tax in provirus-positive cells, revealing that there are quantitative and relative characteristic features among infected cells, primary ATL cells, and cell lines.

Relationship between whole-blood interferon-gamma production and extent of radiographic disease in patients with pulmonary tuberculosis.

The aim of this study was to determine whether whole-blood interferon-gamma (IFN-gamma) production correlates with the radiographic extent of pulmonary tuberculosis before treatment. The subjects were 40 human immunodeficiency virus-negative patients with pulmonary tuberculosis and 36 healthy volunteers. The concentrations of IFN-gamma in whole blood stimulated with Mycobactrium tuberculosis purified protein derivatives (tuberculous PPD) and phytohemagglutinin (PHA) were evaluated. PHA-stimulated IFN-gamma (PHA-IFN-gamma) was lower in the patients than in healthy volunteers (p < 0.05), and inversely correlated with the disease extent (p < 0.01). Tuberculous PPD-stimulated IFN-gamma as a percentage of PHA response (tuberculous PPD-IFN-gamma/PHA-IFN-gamma) was higher in the patients than in healthy volunteers (p < 0.05). However, tuberculous PPD-IFN-gamma/PHA-IFN-gamma did not correlate with the disease extent. Our results indicate that the tuberculous PPD-IFN-gamma/PHA-IFN-gamma may be useful for the diagnosis of tuberculosis but not for evaluating the disease severity, and suggest that PHA-IFN-gamma could be considered as a marker of disease severity.

Suppressor of cytokine signal 3 and IL28 genetic variation predict the viral response to peginterferon and ribavirin.

AIM: The aim of this study was to investigate the relationship among the expression of suppressor of cytokine signaling 3 (SOCS 3) in the liver, the SNPs in the IL28B locus, and the outcome of interferon therapy. METHODS: Prior to interferon treatment, we immunostained 67 liver specimens from chronic hepatitis C (CHC) patients who were receiving peginterferon alpha-2b/ribavirin therapy for suppressor of cytokine signaling 3 (SOCS3), and compared the expression of SOCS3, IL28 polymorphisms and other clinical factors between the patients and compared their eventual outcomes. RESULTS: Significant differences between the low SOCS3 group and high SOCS3 group were found in age, as well as in the platelet, transaminase, gamma-glutamyl transpeptidase levels. The incidence of high SOCS3 was not significantly different between subjects with the TT genotype and the TG genotype (TT : TG = 71%:29%, P = 0.250). In a multivariate analysis, age (≥65 years old) (odds ratio 0.221 [0.120-0.966], P = 0.045), IL28B gene (genotype TT) (odds ratio 5.422 [1.254-23.617], P = 0.024) and SOCS3 (high) (odds ratio 0.308 [0.104-0.948], P = 0.040) were significant predictors of the interferon response. In patients with the TT genotype, those with low SOCS3 immunostaining showed a high sustained virological response (69%), while the sustained virological rate was low (27%) in the patients with high SOCS3 immunostaining. CONCLUSIONS: Using a combination of the SOCS3 immunostained area in the liver and the expression of IL28B single nucleotide polymorphisms might be a useful predictor of hepatitis C virus clearance by interferon therapy.

Adhesion-dependent growth of primary adult T cell leukemia cells with down-regulation of HTLV-I p40Tax protein: a novel in vitro model of the growth of acute ATL cells.

In order to better understand the biology of adult T cell leukemia (ATL), we aimed to establish a novel method, which allows the primary growth of ATL cells using a co-culture system with murine bone marrow-derived stromal cells, MS-5. ATL cells grew in close contact with MS-5 layers and formed so-called "cobblestone areas" (CAs) without the addition of IL-2. In clinical samples, eight of ten (80.0%) cases of acute or lymphoma type ATL cells formed CAs. The frequency of CA forming cells in ATL cells ranged from 0.03 to 1.04%. The morphology, immunophenotyping, and DNA analysis indicated that cells composing CA were compatible with ATL cells, and clonally identical to primary CD4-positive ATL cells. Furthermore, in ATL cells composing CA, the expression of p40Tax was down-regulated in transcriptional and translational level, while that of HTLV-I basic leucine zipper factor (HBZ) gene was comparable to the level of primary ATL cells, resembling expression pattern of proviral genes in in vivo ATL cells. By microarray analysis, several genes which coded products involved in cell-cell interaction, and cellular survival and proliferation, were differentially expressed in ATL cells composing CA compared with primary samples. In conclusion, our co-culture system allows for the first time the growth of primary ATL cells in vitro, and might be useful as an in vitro assay for biological and clinical studies to develop molecular targeting drugs against ATL.