Current opinion in virology最新文献

Influenza viruses are simultaneously supported and antagonized by factors within the host cell. This close relationship is the theoretical basis for future antivirals that target the host rather than the virus itself, a concept termed host-directed therapeutics. Genetic screening has led to the identification of host factors capable of modulating influenza virus infections, and these factors represent candidate targets for host-directed antiviral strategies. Despite advances in understanding host targets, however, there are currently no host-directed interventions for influenza viruses in clinical use. In this brief review, we discuss some host factors identified in knockout/knockdown and overexpression screens that could potentially be targeted as host-directed influenza intervention strategies. We further comment on the feasibility of changing gene expression in the respiratory tract with RNA delivery vectors and transient CRISPR-mediated gene targeting.

Lower and middle-income countries seldom develop vaccines and therapeutics for their own populations and are dependent on supplies from industrialized countries, which are often hampered by financial or supply chain limitations. This has resulted in major delays in delivery with significant loss of life, as seen with the coronavirus pandemic. Since the vast majority of deaths from the antimicrobial resistance crisis are expected to occur in developing countries, there is an urgent need for in-country production of antibacterial therapies such as phages. Nationally controlled phage banks might provide such a solution since locally developed phage therapies tailored to endemic bacterial strains could offer cost-effective antibiotic alternatives.

Bacterial biofilms are involved in many chronic and difficult-to-treat infections. Phage therapy against infectious biofilms is becoming a promising strategy, as suggested by the increasing number of publications demonstrating the efficacy of phages against in vitro formed biofilms. However, the translation between in vitro results to in vivo phage therapy outcome is not straightforward due to the complexity of phage-biofilm interactions in clinical contexts. Here, we provide a critical overview of the in vitro studies of phages for biofilm control of clinical pathogens, followed by the major outcomes and lessons learned from the recently reported case studies (between 2018 and 2021) of phage therapy against biofilm-related infections.

The past decade has provided critical information about the cytoplasmic innate immune sensing pathway of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). These discoveries have broadened our understanding of the interconnectedness of the cGAS-STING pathway with autophagy, programmed cell death, Rig-I-like receptor (RLR) signaling, DNA independent interferon induction, and how this pathway responds to RNA virus infection. These advances highlight how multiple families of RNA viruses are restricted by and in turn have mechanisms to inhibit cGAS-STING dependent type-I interferon (IFN-I) induction. Here we review recent discoveries of how and why the cGAS-STING pathway responds to infection with RNA viruses, novel findings of RNA viral antagonism of the cGAS-STING innate immune sensing pathway, and attempt to provide context for a shift in thinking as to how critical this DNA sensing pathway is for the restriction of a wide range of RNA viruses.

HBV neutralizing antibodies target the viral envelope antigens (HBsAg) and confer long-term immune protection in vaccinees and infected humans who seroconvert. They recognize various HBsAg epitopes, and can be armed with Fc-dependent effector functions essential for eliminating infected cells and stimulating adaptive immunity. Hundreds of HBsAg-specific monoclonal antibodies (mAbs) were produced from the early 80’s, but it is only recently that bona fide human anti-HBV mAbs were generated from vaccinees and seroconverters. Neutralizing HBV mAbs have in vivo prophylactic and therapeutic efficacy in animal models, and the capacity to decrease antigenemia and viremia in infected humans. Thus, polyfunctional, potent and broad human HBV neutralizing mAbs offer novel opportunities to develop effective interventions to prevent and treat HBV infection. Here, we summarize recent findings on the humoral immune response to HBV, and explore the potential of human HBV neutralizing mAbs as immunotherapeutics to help achieving a functional cure for HBV.

The pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) is a continuing worldwide threat to human health and social economy. Historically, SARS-CoV-2 follows SARS and MERS as the third coronavirus spreading across borders and continents, but far more dangerous with long-lasting symptomatic consequences. The current situation is strong evidence that coronaviruses will continue to be pathogens of consequence in the future, thus calling for the development of neutralizing antibody-based prophylactics and therapeutics for prevention and treatment of COVID-19 and other human coronavirus diseases. This review summarized the progresses of developing neutralizing monoclonal antibodies against infection of SARS-CoV-2, SARS-CoV, and MERS-CoV, and discussed their potential applications in prevention and treatment of COVID-19 and other human coronavirus diseases.

Rabies is a severe viral infection that causes an acute encephalomyelitis, which presents a case fatality of nearly 100% after the manifestation of neurological clinical signs. Rabies can be efficiently prevented with post-exposure prophylaxis (PEP), composed of vaccines and anti-rabies immunoglobulins (RIGs); however, no treatment exists for symptomatic rabies. The PEP protocol faces access and implementation obstacles in resource-limited settings, which could be partially overcome by substituting RIGs for monoclonal antibodies (mAbs). mAbs offer lower production costs, consistent supply availability, long-term storage/stability, and an improved safety profile. Here we summarize the key features of the different available mAbs against rabies, focusing on their application in PEP and highlighting their potential in a novel therapeutic approach.

The vertebrate interferon (IFN) response controls viral infections by inducing hundreds of interferon-stimulated genes (ISGs), many of which encode ‘restriction factors’ that uniquely target certain viruses. ISG studies have historically had a human-centric focus, which is justified because these natural defense mechanisms might be leveraged to treat human viral disease. However, certain mammals are reservoirs for zoonotic viruses that can ‘spill over’ into humans. Additionally, restriction factors have prominent roles in the ongoing evolutionary genetic conflicts between viruses and their hosts. Thus, there is a growing need to understand antiviral IFN/ISG responses in other species, particularly in known reservoirs of zoonotic viruses. This review focuses on functional and evolutionary insight into antiviral IFN responses that have been obtained from studying non-model mammalian species.

The SARS-CoV-2 pandemic that struck in 2019 has left the world crippled with hundreds of millions of cases and millions of people dead. During this time, we have seen unprecedented support and collaboration amongst scientists to respond to this deadly disease. Advances in the field of structural biology, in particular cryoEM and cryo-electron tomography, have allowed unprecedented structural analysis of SARS-CoV-2. Here, we review the structural work on the SARS-CoV-2 virus and viral components, as well as its cellular assembly process, highlighting some important structural findings that have made significant impact on the protection from and treatment of emerging viral infections.