Current opinion in virology最新文献

Anelloviridae and Redondoviridae are virus families with small, circular, single-stranded DNA genomes that are common components of the human virome. Despite their small genome size of less than 5000 bases, they are remarkably successful — anelloviruses colonize over 90% of adult humans, while the recently discovered redondoviruses have been found at up to 80% prevalence in some populations. Anelloviruses are present in blood and many organs, while redondoviruses are found mainly in the ororespiratory tract. Despite their high prevalence, little is known about their biology or pathogenic potential. In this review, we discuss anelloviruses and redondoviruses and explore their enigmatic roles in human health and disease.

Persistent virus infections are achieved when the intricate balance of virus replication, host-cell division and successful immune evasion is met. The genomes of persistent DNA viruses are either maintained as extrachromosomal episomes or can integrate into the host genome. Common to both these strategies of persistence is the chromatinisation of viral DNA by cellular histones which, like host DNA, are subject to epigenetic modification. Epigenetic repression of viral genes required for lytic replication occurs, while genes required for latent or persistent infection are maintained in an active chromatin state. Viruses utilise host-cell chromatin insulators, which function to maintain epigenetic boundaries and enforce this strict transcriptional programme. Here, we review insulator protein function in virus transcription control, focussing on CCCTC-binding factor (CTCF) and cofactors. We describe CTCF-dependent activities in virus transcription regulation through epigenetic and promoter–enhancer insulation, three-dimensional chromatin looping and manipulation of transcript splicing.

Kaposi sarcoma herpesvirus (KSHV)-associated diseases (Kaposi sarcoma, multicentric Castleman disease, primary effusion lymphoma, and KSHV inflammatory cytokine syndrome) are associated with immune suppression and dysregulation and loss of KSHV-specific immunity. These diseases are most frequent in people living with HIV as well as those with primary or iatrogenic immune deficiencies. KSHV itself can modulate the immune system via viral homologs of host cytokines or downregulation of immune-surface markers altering host immune surveillance. These factors make KSHV-associated diseases prime targets for immunotherapy approaches. Several agents have been studied or are under investigation in KSHV-associated diseases, including monoclonal antibodies, immunomodulatory agents, and therapeutic cytokines. Here, we review the role of immunotherapies in KSHV-associated diseases.

Potent broadly neutralizing antibodies (bNAbs) targeting HIV-1 exhibit significant antiviral activity in humans. Recent advances have demonstrated that novel antibodies and bNAb combinations can effectively restrict the development of viral escape mutations. Moreover, passive immunization trials have provided proof-of-principle for bNAb-mediated prevention of infection with antibody-sensitive HIV-1 strains. In contrast, clinical studies investigating the activity of HIV-1 bNAbs on the latent reservoir failed to demonstrate substantial effects. Clinical adoption of HIV-1 bNAbs will require the development of more potent and broadly active antibodies as well as their implementation in optimized strategies to fully harness the capabilities of bNAbs. We review preclinical and clinical studies on HIV-1 bNAbs to highlight their potential and remaining limitations.

Despite the growing interest in the microbiome in recent years, the study of the virome, the major part of which is made up of bacteriophages, is relatively underdeveloped compared with their bacterial counterparts. This is due in part to the lack of a universally conserved marker such as the 16S rRNA gene. For this reason, the development of metagenomic approaches was a major milestone in the study of the viruses in the microbiome or virome. However, it has become increasingly clear that these wet-lab methods have not yet been able to detect the full range of viruses present, and our understanding of the composition of the virome remains incomplete. In recent years, a range of new technologies has been developed to further our understanding. Direct RNA-Seq technologies bypass the need for cDNA synthesis, thus avoiding biases subjected to this step, which further expands our understanding of RNA viruses. The new generation of amplification methods could solve the low biomass issue relevant to most virome samples while reducing the error rate and biases caused by whole genome amplification. The application of long-read sequencing to virome samples can resolve the shortcomings of short-read sequencing in generating complete viral genomes and avoid the biases introduced by the assembly. Novel experimental methods developed to measure viruses' host range can help overcome the challenges of assigning hosts to many phages, specifically unculturable ones.

Picobirnaviruses are small double-stranded RNA viruses first discovered in 1988 in stool samples from patients with diarrhea. It has generally been assumed that picobirnaviruses infect animal hosts and that they are potential agents of diarrhea, but there is still no direct evidence demonstrating that picobirnaviruses infect animals. In the metagenomic era, virome studies have broadened our understanding of picobirnavirus genetic diversity and genome organization, expanded the types of animals in which they have been detected, and identified novel associations with human disease. Most importantly, from the wealth of new sequencing data and comparative genomic analyses, a provocative new hypothesis has emerged that picobirnaviruses may not infect animals, but rather that they may infect evolutionarily simpler denizens of the gastrointestinal tract: bacteria and/or fungi. Depending on whether the true hosts of picobirnaviruses are animals, fungi, or bacteria, the mechanisms by which they impact animal biology will vary dramatically.

Asymmetric structural elements are typically not readily visualized in icosahedral viruses that have other obvious symmetrical features and most asymmetry has gone unresolved for decades. Asymmetric features may be incorporated during assembly or maturation or develop during key steps in the infectious cycle of the virus. However, resolving asymmetric features requires abandoning capsid-wide symmetry averaging and relying on special applications during single-particle cryogenic electron microscopy (cryo-EM) analysis. Thanks to the advances in the cryo-EM field, we are learning more about asymmetry of viruses. Here we summarize some of what is currently known about asymmetric structural features using as examples members of the Togaviridae, Flaviviridae, Herpesviridae, Parvoviridae, and Papillomaviridae.