Coxsackievirus-B4E2 can infect monocytes and macrophages in vitro and in vivo

International audienceViral RNA (vRNA) is found in mice inoculated with coxsackievirus-B4E2 (CV-B4E2). The CV-B4E2 infection of murine spleen cells in vitro is enhanced with CV-B4E2-infected mouse serum. It has been investigated whether monocyte/macrophages were targets of CV-B4E2 in mice. vRNA has been detected in spleen and bone marrow of infected animals. The levels of vRNA were higher in CD14 + cells than in CD14- spleen cells and in F4/80- cells than in F4/80 + spleen cells. Meanwhile, CD14 + cells and F4/80- cells were more permissive to CV-B4E2 in vitro and the infection was enhanced when the virus was mixed with immune serum. While CV-B4E2 infected BMDM cultures (98% F4/80 +); however, the immune serum did not enhance the infection. In conclusion, CV-B4E2 infects monocytes (CD14 +, F4/80-) and macrophages (CD14 +, F4/80 +) in vivo and immune serum can enhance the in vitro infection of these cells arising out of the spleen

Impaired Functional T-Cell Response to SARS-CoV-2 After Two Doses of BNT162b2 mRNA Vaccine in Older People

International audienceLong-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4+- and CD8+-specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older (n = 54) compared with the COVID-19-naive younger adults (n = 121). Notably, older participants’ neutralizing antibodies were 10 times lower than the younger’s antibody titers (p < 0.0001) and LCTF residents also had an impaired functional T-cell response: the frequencies of IFNγ+ and IFNγ+IL-2+TNFα+ cells among specific CD4+ T cells, and the frequency of specific CD8+ T cells were lower in COVID-19-naive older participants than in COVID-19-naive young adults (p < 0.0001 and p = 0.0018, respectively). However, COVID-19-recovered older participants (n = 51) had greater antibody and T-cell responses, including IFNγ+ and IFNγ+IL-2+TNFα+-specific CD4+ T cells (p < 0.0001), as well as TNFα+-specific CD8+ T cells (p < 0.001), than COVID-19-naive older adults. We also observed that “inflammageing” and particularly high plasma levels of TNFα was associated to poor antibody response in the older participants. In conclusion, our results show that the COVID-19-naive older people had low counts and impaired specific CD4+ and CD8+ T cells, in addition to impaired antibody response, and that specific studies are warranted to assess the efficiency of SARS-CoV-2 mRNA-based vaccines, as in other immunocompromised subjects. Our study also shows that, despite their physiological alterations of immunity, vaccination is highly efficient in boosting the prior natural memory response in COVID-19-recovered older people

Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants

Background & Aims: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBV patients infected with different genotypes. Methods: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. Results: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83–0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94–0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. Conclusions: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients

Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

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Viral infections in type 1 diabetes mellitus-why the beta cells?

Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection-particularly by enteroviruses (for example, coxsackievirus)-as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.SCOPUS: re.jinfo:eu-repo/semantics/publishe