Egress of HSV-1 capsid requires the interaction of VP26 and a cellular tetraspanin membrane protein

HSV-1 viral capsid maturation and egress from the nucleus constitutes a self-controlled process of interactions between host cytoplasmic membrane proteins and viral capsid proteins. In this study, a member of the tetraspanin superfamily, CTMP-7, was shown to physically interact with HSV-1 protein VP26, and the VP26-CTMP-7 complex was detected both in vivo and in vitro. The interaction of VP26 with CTMP-7 plays an essential role in normal HSV-1 replication. Additionally, analysis of a recombinant virus HSV-1-UG showed that mutating VP26 resulted in a decreased viral replication rate and in aggregation of viral mutant capsids in the nucleus. Together, our data support the notion that biological events mediated by a VP26 - CTMP-7 interaction aid in viral capsid enveloping and egress from the cell during the HSV-1 infectious process

Comparison analysis of microRNAs in response to EV71 and CA16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms

AbstractHand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) infections which presented significantly different clinical manifestations. Nevertheless, the factors underlying these differences remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. Here, we performed comprehensive miRNA profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at multiple time points using high-throughput sequencing. The results showed that 154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 56 known differentially expressed miRNAs by further screening for targets prediction. GO and pathway analysis of these targets demonstrated that 18 biological processes, 7 molecular functions, 1 cellular component and 123 pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt signalling pathway and angiogenesis showed significant alterations. The regulatory networks of these miRNAs with predicted targets, GOs, pathways and transcription factors were determined, which suggested that miRNAs displayed intricate regulatory mechanisms during the infection phase. Consequently, we specifically analysed the hierarchical GO categories of the predicted targets involved in adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to airway epithelial barrier function. Taken together, our data provide useful insights that help elucidate the different host-pathogen interactions following EV71 and CA16 infection and might offer novel therapeutic targets for these infections

Neonatal rhesus monkey is a potential animal model for studying pathogenesis of EV71 infection

AbstractData from limited autopsies of human patients demonstrate that pathological changes in EV71-infected fatal cases are principally characterized by clear inflammatory lesions in different parts of the CNS; nearly identical changes were found in murine, cynomolgus and rhesus monkey studies which provide evidence of using animal models to investigate the mechanisms of EV71 pathogenesis. Our work uses neonatal rhesus monkeys to investigate a possible model of EV71 pathogenesis and concludes that this model could be applied to provide objective indicators which include clinical manifestations, virus dynamic distribution and pathological changes for observation and evaluation in interpreting the complete process of EV71 infection. This induced systemic infection and other collected indicators in neonatal monkeys could be repeated; the transmission appears to involve infecting new monkeys by contact with feces of infected animals. All data presented suggest that the neonatal rhesus monkey model could shed light on EV71 infection process and pathogenesis

Risk Factors for Long COVID in Older Adults

As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating. Within this context, the elderly population has not only become susceptible and high-risk during the acute phase of COVID-19 but also has considerable risks when confronting long COVID. Elderly individuals possess specific immunological backgrounds, and during the process of aging, their immune systems can enter a state known as “immunosenescence”. This further exacerbates “inflammaging” and the development of various comorbidities in elderly individuals, rendering them more susceptible to long COVID. Additionally, long COVID can inflict both physical and mental harm upon elderly people, thereby reducing their overall quality of life. Consequently, the impact of long COVID on elderly people should not be underestimated. This review seeks to summarize the infection characteristics and intrinsic factors of older adults during the COVID-19 pandemic, with a focus on the physical and mental impact of long COVID. Additionally, it aims to explore potential strategies to mitigate the risk of long COVID or other emerging infectious diseases among older adults in the future

Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines

Hand-foot-and-mouth disease (HFMD) is an infectious disease of children caused by more than 20 types of enteroviruses, with most cases recovering spontaneously within approximately one week. Severe HFMD in individual children develops rapidly, leading to death, and is associated with other complications such as viral myocarditis and type I diabetes mellitus. The approval and marketing of three inactivated EV-A71 vaccines in China in 2016 have provided a powerful tool to curb the HFMD epidemic but are limited in cross-protecting against other HFMD-associated enteroviruses. This review focuses on the epidemiological analysis of HFMD-associated enteroviruses since the inactivated EV-A71 vaccine has been marketed, collates the progress in the development of multivalent enteroviruses vaccines in different technical routes reported in recent studies, and discusses issues that need to be investigated for safe and effective HFMD multivalent vaccines

Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines

Hand-foot-and-mouth disease (HFMD) is an infectious disease of children caused by more than 20 types of enteroviruses, with most cases recovering spontaneously within approximately one week. Severe HFMD in individual children develops rapidly, leading to death, and is associated with other complications such as viral myocarditis and type I diabetes mellitus. The approval and marketing of three inactivated EV-A71 vaccines in China in 2016 have provided a powerful tool to curb the HFMD epidemic but are limited in cross-protecting against other HFMD-associated enteroviruses. This review focuses on the epidemiological analysis of HFMD-associated enteroviruses since the inactivated EV-A71 vaccine has been marketed, collates the progress in the development of multivalent enteroviruses vaccines in different technical routes reported in recent studies, and discusses issues that need to be investigated for safe and effective HFMD multivalent vaccines

Influenza and Universal Vaccine Research in China

Influenza viruses usually cause seasonal influenza epidemics and influenza pandemics, resulting in acute respiratory illness and, in severe cases, multiple organ complications and even death, posing a serious global and human health burden. Compared with other countries, China has a large population base and a large number of influenza cases and deaths. Currently, influenza vaccination remains the most cost-effective and efficient way to prevent and control influenza, which can significantly reduce the risk of influenza virus infection and serious complications. The antigenicity of the influenza vaccine exhibits good protective efficacy when matched to the seasonal epidemic strain. However, when influenza viruses undergo rapid and sustained antigenic drift resulting in a mismatch between the vaccine strain and the epidemic strain, the protective effect is greatly reduced. As a result, the flu vaccine must be reformulated and readministered annually, causing a significant drain on human and financial resources. Therefore, the development of a universal influenza vaccine is necessary for the complete fight against the influenza virus. By statistically analyzing cases related to influenza virus infection and death in China in recent years, this paper describes the existing marketed vaccines, vaccine distribution and vaccination in China and summarizes the candidate immunogens designed based on the structure of influenza virus, hoping to provide ideas for the design and development of new influenza vaccines in the future

Subgenomic RNAs and Their Encoded Proteins Contribute to the Rapid Duplication of SARS-CoV-2 and COVID-19 Progression

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently widespread throughout the world, accompanied by a rising number of people infected and breakthrough infection of variants, which make the virus highly transmissible and replicable. A comprehensive understanding of the molecular virological events and induced immunological features during SARS-CoV-2 replication can provide reliable targets for vaccine and drug development. Among the potential targets, subgenomic RNAs and their encoded proteins involved in the life cycle of SARS-CoV-2 are extremely important in viral duplication and pathogenesis. Subgenomic RNAs employ a range of coping strategies to evade immune surveillance from replication to translation, which allows RNAs to synthesize quickly, encode structural proteins efficiently and complete the entire process of virus replication and assembly successfully. This review focuses on the characteristics and functions of SARS-CoV-2 subgenomic RNAs and their encoded proteins and explores in depth the role of subgenomic RNAs in the replication and infection of host cells to provide important clues to the mechanism of COVID-19 pathogenesis