Current opinion in virology最新文献

Ebola virus (EBOV) outbreaks can claim thousands of lives, cripple healthcare systems and local economies. Effective vaccines and treatments against EBOV are therefore needed to limit the impact of this deadly disease. In 2019, a hallmark clinical trial demonstrated the efficacy of monoclonal antibody (mAb) against EBOV. Despite, this recent success, survival of individuals with high viremia remains low. Effective immunotherapies against other Ebolavirus species are still under pre-clinical development. More importantly, the cost of immunotherapies is prohibitive to most individual and affected countries. Novel manufacturing and administration strategies of mAb protein or genetic information could substantially reduce the cost of immunotherapies; hence making them valuable tools against EBOV and other infectious agents.

Bats are the natural reservoir host for a number of zoonotic viruses, including Hendra and Nipah viruses of Henipavirus genus, which are highly pathogenic in humans and numerous other mammalian species. Despite being infected, bats present limited signs of disease but still retain the ability to transmit the infection to other susceptible hosts, presenting thus a permanent source of new viral outbreaks. Different mechanisms have evolved in fruit bats permitting them to efficiently control the Henipavirus infection. These mechanisms likely allow bats to establish an adequate equilibrium between viral tolerance and antiviral defense, enabling them thus to avoid both uncontrollable virus expansion as well as immunopathology linked to excessive antiviral responses.

The ease with which bacteria can evolve resistance to phages is a key consideration for development of phage therapy. Here, we review recent work on the different evolutionary and ecological approaches to mitigate the problem. The approaches are broadly categorised into two areas: Minimising evolved phage resistance; and Directing phage-resistance evolution towards therapeutically beneficial outcomes.

Viruses are diverse biological entities that influence all life. Even with limited genome sizes, viruses can manipulate, drive, steal from, and kill their hosts. The field of virus genomics, using sequencing data to understand viral capabilities, has seen significant innovations in recent years. However, with advancements in metagenomic sequencing and related technologies, the bottleneck to discovering and employing the virosphere has become the analysis of genomes rather than generation. With metagenomics rapidly expanding available data, vital components of virus genomes and features are being overlooked, with the issue compounded by lagging databases and bioinformatics methods. Despite the field moving in a positive direction, there are noteworthy points to keep in mind, from how software-based virus genome predictions are interpreted to what information is overlooked by current standards. In this review, we discuss conventions and ideologies that likely need to be revised while continuing forward in the study of virus genomics.

Influenza viruses cause occasional pandemics and annual epidemics, thus persist as a threat to human society. The high variability of viral envelope proteins resulting from antigenic shift and antigenic drift allows influenza viruses to escape human herd immunity. During the past decade, along with the breakthroughs of human monoclonal antibody technologies, many broad reactive monoclonal antibodies (mAbs) that neutralize diverse influenza subtypes have been isolated and characterized. The achievements in this field have provided potential candidates of anti-influenza therapeutics and shed light on the design of universal influenza vaccines. Here, we review the broad neutralizing antibodies (bnAbs) targeting the virus surface proteins, summarize their epitopes, broad spectrum and immunological mechanisms of action and discuss the design of universal influenza vaccines inspired by bnAbs.

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.

A hallmark feature of lentiviruses, which separates them from other members of the retrovirus family, is their ability to infect non-dividing cells by traversing the nuclear pore complex. The viral determinant that mediates HIV-1 nuclear import is the viral capsid (CA) protein, which forms the conical core protecting the HIV-1 genome in a mature virion. Recently, a series of novel approaches developed to monitor post-fusion events in infection have challenged previous textbook models of the viral life cycle, which envisage reverse transcription and disassembly of the capsid core as events that complete in the cytoplasm. In this review, we summarize these recent findings and describe their implications on our understanding of the spatiotemporal staging of HIV-1 infection with a focus on the nuclear import and its implications in other aspects of the viral lifecycle.

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.