Role of the receptor for activated C kinase 1 during viral infectionWang, Yan; Qiao, Xiaorong; Li, Yuhan; Yang, Qingru; Wang, Lulu; Liu, Xiaolan; Wang, Hua; Shen, Hongxing
doi: 10.1007/s00705-022-05484-wpmid: 35763066
Viruses can survive only in living cells, where they depend on the host’s enzymatic system for survival and reproduction. Virus–host interactions are complex. On the one hand, hosts express host-restricted factors to protect the host cells from viral infections. On the other hand, viruses recruit certain host factors to facilitate their survival and transmission. The identification of host factors critical to viral infection is essential for comprehending the pathogenesis of contagion and developing novel antiviral therapies that specifically target the host. Receptor for activated C kinase 1 (RACK1), an evolutionarily conserved host factor that exists in various eukaryotic organisms, is a promising target for antiviral therapy. This review primarily summarizes the roles of RACK1 in regulating different viral life stages, particularly entry, replication, translation, and release.
Mechanisms of host type I interferon response modulation by the nucleocapsid proteins of alpha- and betacoronavirusesYelemali, Priya; Hao, Lin; Liu, Qiang
doi: 10.1007/s00705-022-05513-8pmid: 35763067
Coronaviruses can have a devastating impact on the health of humans and animals. Porcine epidemic diarrhea virus (PEDV) causes extremely high fatality rates in neonatal piglets, whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic in humans. As a critical component of the host antiviral innate immune response, type I interferon production and signaling play a very important role, especially in the initial phase of the antiviral responses. Coronaviruses have evolved multiple ways to counteract type I interferon responses. Although the primary functions of the nucleocapsid protein are to facilitate viral RNA replication and package viral genomic RNA into virions, recent studies have shown that the nucleocapsid protein is also involved in virus-host interactions. The aim of this review is to summarize our current understanding of how the nucleocapsid proteins of PEDV and SARS-CoV-2 modulate type I interferon responses. This knowledge will be useful for developing strategies to combat coronavirus infections.
Molecular mechanisms involved in anosmia induced by SARS-CoV-2, with a focus on the transmembrane serine protease TMPRSS2Karimian, Ali; Behjati, Mohaddeseh; Karimian, Mohammad
doi: 10.1007/s00705-022-05545-0pmid: 35939103
Since 2020, SARS-CoV-2 has caused a pandemic virus that has posed many challenges worldwide. Infection with this virus can result in a number of symptoms, one of which is anosmia. Olfactory dysfunction can be a temporary or long-term viral complication caused by a disorder of the olfactory neuroepithelium. Processes such as inflammation, apoptosis, and neuronal damage are involved in the development of SARS-CoV-2-induced anosmia. One of the receptors that play a key role in the entry of SARS-CoV-2 into the host cell is the transmembrane serine protease TMPRSS2, which facilitates this process by cleaving the viral S protein. The gene encoding TMPRSS2 is located on chromosome 21. It contains 15 exons and has many genetic variations, some of which increase the risk of disease. Delta strains have been shown to be more dependent on TMPRSS2 for cell entry than Omicron strains. Blockade of this receptor by serine protease inhibitors such as camostat and nafamostat can be helpful for treating SARS-CoV-2 symptoms, including anosmia. Proper understanding of the different functional aspects of this serine protease can help to overcome the therapeutic challenges of SARS-CoV-2 symptoms, including anosmia. In this review, we describe the cellular and molecular events involved in anosmia induced by SARS-CoV-2 with a focus on the function of the TMPRSS2 receptor.
Maintenance of Epstein-Barr virus latency through interaction of LMP2A with CXCR4Qin, Ni; Zhang, Yan; Xu, Lin; Liu, Wen; Luo, Bing
doi: 10.1007/s00705-022-05511-wpmid: 35752684
Epstein-Barr virus (EBV) belongs to the subfamily Gammaherpesvirinae and was the first human tumor virus to be discovered. The global rate of EBV infection in adults exceeds 90%. EBV can participate in the regulation of multiple genes and signal pathways through its latency genes. Many studies have shown that CXCR4 is involved in the development of gastric cancer, but there have been few studies on the specific mechanisms involved in EBV-associated gastric cancer (EBVaGC). In this study, we explored the mechanism by which EBV-encoded products maintain latent EBV infection through interaction with CXCR4 and investigated the role of CXCR4 in EBV-positive cells. The results show that there is a positive feedback between the EBV-encoded products and CXCR4, and LMP2A can activate CXCR4 through the NF-κB pathway. In addition, CXCR4 can be fed back to LMP2A and EBNA1 through the ERK signaling pathway. At the same time, CXCR4 can promote the proliferation and migration of EBV-positive cells, reduce the expression of the immediate early protein BZLF1, the late protein EBV gp350, and the viral capsid antigen, and play an important role in maintaining the incubation period of EBV infection. These findings are applicable to the further targeted therapy of EBVaGC.
Multiple isoforms of HSP70 and HSP90 required for betanodavirus multiplication in medaka cellsZenke, Kosuke; Okinaka, Yasushi
doi: 10.1007/s00705-022-05489-5pmid: 35752988
Heat shock proteins (HSPs) are molecular chaperones that have recently been shown to function as host factors (HFs) for virus multiplication in fish as well as in mammals, plants, and insects. HSPs are classified into families, and each family has multiple isoforms. However, no comprehensive studies have been performed to clarify the biological importance of these multiple isoforms for fish virus multiplication. Betanodaviruses are the causative agents of viral nervous necrosis in cultured marine fish and cause very high mortality. Although the viral genome and encoded proteins have been characterized extensively, information on HFs for these viruses is limited. In this study, therefore, we focused on the HSP70 and HSP90 families to examine the importance of their isoforms for betanodavirus multiplication. We found that HSP inhibitors (17-AAG, radicicol, and quercetin) suppressed viral RNA replication and production of progeny virus in infected medaka (Oryzias latipes) cells. Thermal stress or virus infection resulted in increased expression of some isoform genes and facilitated virus multiplication. Furthermore, overexpression and knockdown of some isoform genes revealed that the isoforms HSP70-1, HSP70-2, HSP70-5, HSP90-α1, HSP90-α2, and HSP90-β play positive roles in virus multiplication in medaka. Collectively, these results suggest that multiple isoforms of fish HPSs serve as HFs for betanodavirus multiplication.
Urolithin A inhibits enterovirus 71 replication and promotes autophagy and apoptosis of infected cells in vitroWang, Shengyu; Qiao, Junhua; Chen, Yaping; Tian, Langfei; Sun, Xin
doi: 10.1007/s00705-022-05471-1pmid: 35790643
Hand, foot, and mouth disease (HFMD) is a serious threat to the health of infants, and it can be caused by enterovirus 71 (EV71). The clinical symptoms are mostly self-limiting, but some infections develop into aseptic meningitis with poor prognosis and even death. In this study, urolithin A (UroA), an intestinal metabolite of ellagic acid, significantly inhibited the replication of EV71 in cells. Further evaluation showed that UroA was better than ribavirin in terms of its 50% cytopathic concentration (CC50), 50% inhibitory concentration (IC50), and selectivity index. Moreover, UroA inhibited the proliferation of EV71 by promoting autophagy and apoptosis of infected cells. Therefore, UroA is a candidate drug for the treatment of EV71 infection.
Effect of probiotic bacteria on porcine rotavirus OSU infection of porcine intestinal epithelial IPEC-J2 cellsLeblanc, Danielle; Raymond, Yves; Lemay, Marie-Josée; Champagne, Claude P.; Brassard, Julie
doi: 10.1007/s00705-022-05510-xpmid: 35794494
Rotavirus infections in nursing or post-weaning piglets are known to cause diarrhea, which can lead to commercial losses. Probiotic supplementation is used as a prophylactic or therapeutic approach to dealing with microbial infections in humans and animals. To evaluate the effect of probiotic bacteria on porcine rotavirus infections, non-transformed porcine intestinal epithelial IPEC-J2 cells were used as an in vitro model, and three different procedures were tested. When cells were exposed to seven probiotics at concentrations of 105, 106, or 107 CFU/mL for 16 h and removed before rotavirus challenge, infection reduction rates determined by flow cytometry were as follows: 15% (106) and 18% (105) for Bifidobacterium longum R0175, 15% (107) and 16% (106) for B. animalis lactis A026, and 15% (105) for Lactobacillus plantarum 299V. When cells were exposed to three selected probiotic strains for 1 h at higher concentrations, that is, 108 and 5 × 108 CFU/mL, before infection with rotavirus, no significant reduction was observed. When the probiotic bacteria were incubated with the virus before cell infection, a significant 14% decrease in the infection rate was observed for B. longum R0175. The results obtained using a cell-probiotics-virus platform combined with flow cytometry analysis suggest that probiotic bacteria can have a protective effect on IPEC-J2 cells before infection and can also prevent rotavirus infection of the cells.
Genomic analysis of a novel active prophage of Hafnia paralveiPan, Lingting; Li, Dengfeng; Lin, Wei; Liu, Wencai; Qin, Weinan; Xu, Lihua; Tong, Yigang
doi: 10.1007/s00705-022-05498-4pmid: 35752683
Little is known about the prophages in Hafniaceae bacteria. A novel Hafnia phage, yong2, was induced from Hafnia paralvei by treatment with mitomycin C. The phage has an elliptical head with dimensions of approximately 45 × 38 nm and a long noncontractile tail of approximately 157 × 4 nm. The complete genome of Hafnia phage yong2 is a 39,546-bp double-stranded DNA with a G+C content of 49.9%, containing 59 open reading frames (ORFs) and having at least one fixed terminus (GGGGCAGCGACA). In phylogenetic analysis, Hafnia phage yong2 clustered with four predicted Hafnia prophages and one predicted Enterobacteriaceae prophage. These prophages and members of the family Drexlerviridae together formed two distinct subclades nested within a clade, suggesting the existence of a novel class of prophages with conserved sequences and a unique evolutionary status not yet studied before in Hafniaceae and Enterobacteriaceae bacteria.