Uirusu最新文献

Human norovirus (HuNoV) is an infectious virus that accounts for more than half of all cases of infectious gastroenteritis, but its mechanism of infection and multiplication within the host are largely unknown. Accordingly, there are no available vaccines or specific therapeutic agents　applicable to HuNoV infection. The primary reason for this is the absence of an established in vitro culture and growth system for HuNoV. Therefore, virological analysis of HuNoV has been conducted using murine norovirus, which is most closely related to HuNoV and can be cultured in some cell-lines. Recently, several laboratories have reported successful in vitro cultivation of HuNoV using human intestinal epithelial cells, raising expectations for further advancements in HuNoV research. In this paper, we present recent findings regarding the in vitro propagation system of HuNoV.  .

Cytotoxic T lymphocytes (CTLs) play an important role in the control of various viral infection. CTLs recognize a complex of HLA (human leukocyte antigen) class I molecule and epitope peptide derived from viral protein on the cell surface via T cell receptors and can destroy virally infected cells. It is becoming evident that SARS-CoV-2 specific T cells play a crucial role in the control of COVID-19. We characterized T cells specific for various SARS-CoV-2 variants and identified that a L452R mutation in the Delta spike protein evades HLA-A*24:02-restricted T cell responses and increases virus infectivity. In contrast, HLA-A*24:02-restricted T cells strongly suppresses Omicron BA.1 replication due to a G446S mutation, located just outside the N-terminus of the cognate epitope, in the Omicron BA.1 variant via enhanced antigen processing and presentation of the epitope. These data indicate that T cell specific for antigens derived from variable regions is highly susceptible for the mutation and its location. The detail analysis of antigen-specific T cell responses toward variants provides better insights for the rational design of vaccine antigens or immunotherapy to induce efficient cellular immunity against new emerging viruses/variants.

Epstein-Barr virus (EBV) is a ubiquitous human lymphotropic herpesvirus that causes several malignancies. EBV infects approximately 90% of individuals worldwide. Recent studies have provided robust evidence for a causal role of EBV in multiple sclerosis. Multiple sclerosis is the most prevalent chronic inflammatory and degenerative disease of the central nerve system (CNS) that progresses over time to progressive neurodegeneration and disability. Here, I review how a ubiquitous virus can elicit autoreactive antibodies through molecular mimicry between viral and host CNS antigens, triggering multiple sclerosis.

Although the current hepatitis B (HB) vaccine comprising yeast-derived small hepatitis B surface antigen (HBsAg) is potent and safe and used worldwide, specific concerns should not be ignored, such as the attenuated prophylaxis against hepatitis B virus (HBV) infection with specific amino acid polymorphisms, called vaccine-escape mutations (VEMs). We investigated a novel HB vaccine consisting of large-HBsAg that covers the shortcomings of the current HB vaccine in a nonhuman primate model. The yeast-derived large-HBsAg was mixed with the adjuvant and used to immunize rhesus macaques, and the induction of antibodies to HBsAg was compared with that of the current HB vaccine. The current HB vaccine predominantly induced antibodies to small-HBsAg, whereas immunization with the large-HBsAg vaccine mainly induced antibodies to the preS1 region. Although the antibodies induced by the current HB vaccine could not prevent infection of HBV with VEMs, the large-HBsAg vaccine-induced antibodies neutralized infection of HBV with VEMs at levels similar to those of the wild type. The HBV genotypes that exhibited attenuated neutralization by induced antibodies differed between these vaccines. In conclusion, the novel HB vaccine consisting of large-HBsAg was revealed to be useful to compensate for shortcomings of the current HB vaccine. The combined use of these HB vaccines may be able to induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes.

More than 40 years after the discovery of human sapovirus (HuSaV), we have established a HuSaV culture system in which HuTu80 cells derived from the human duodenum adenocarcinoma cell line are cultured together with the addition of bile acid as a supplement. In addition to being a common cell line, this system using HuTu80 cells is a versatile method because classical culture media are available, and it is easy to scale-up for culture. However, the number of culture days required to obtain sufficient viral titer, the confirmation of viral gene conservation for sample selection, and the method for passaging of HuTu80-cells were crucial. So far, 15 genotypes have been successfully propagated and stocked, and stable supply as research resources has been achieved. Due to the above efforts, we can now proceed with the production and analysis of antisera using purified antigens and the evaluation of inactivation conditions. This manuscript introduces the background for selection of the cell line and bile acids, and the topics that have been discussed since the publication, as well as future issues that were raised such as the expression of cytopathicity and elucidation of low UV-C sensitivity of fecal-derived HuSaV.