Current Opinion in Virology

Viral-associated cancers are a distinct group of malignancies with a unique pathogenesis and epidemiology. Liquid biopsy is a minimally invasive way to identify tumor-associated abnormalities in blood derivatives, such as plasma, to guide the diagnosis, prognosis, and treatment of patients with cancer. Liquid biopsy encompasses a multitude of circulating analytes with the most extensively studied being cell-free DNA (cfDNA). In recent decades, substantial advances have been made toward the study of circulating tumor DNA in nonviral-associated cancers...

Flagellin is the cognate ligand for host pattern recognition receptors, toll-like receptor 5 (TLR5) in the cell surface, and NAIP5/NLRC4 inflammasome in the cytosol. TLR5-binding domain is located in D1 domain, where crucial amino acid sequences are conserved among diverse bacteria. The highly conserved C-terminal 35 amino acids of flagellin were proved to be responsible for the inflammasome activation by binding to NAIP5. D2/D3 domains, located in the central region and exposed to the outside surface of flagellar filament, are heterogeneous across bacterial species and highly immunogenic...

The type I interferon response is critical for controlling viral infection and triggers the production of downstream-target genes, termed interferon-stimulated genes (ISGs). While ISGs have a plethora of ways to restrict viruses at different stages of their replication cycle, they are also important to dampen immune responses to avoid tissue damage in the case of exuberant effects. However, this counter regulation of the immune response comes with the downside that it can open a door for viruses to get a foothold in their host...

Cytomegalovirus (CMV) is a ubiquitous herpesvirus that has a profound impact on the host immune system. Congenital cytomegalovirus (cCMV) infection modulates neonatal immune cell compartments, yet the full impact of in utero exposure on developing fetal immune cells remains poorly characterized. A series of recent studies have identified a potential link between cCMV infection and the development of acute lymphoblastic leukemia (ALL) in childhood. Here, we review the emerging evidence linking CMV and ALL risk, discuss what is known about the causes of childhood ALL, and propose how CMV infection in early life may confer increased ALL risk...

Cytomegaloviruses (CMVs) are typically disseminated by cell-to-cell transfer, which requires reprogramming of cellular signaling pathways and restructuring of the cell architecture. Viral particles not only transfer genetic information between cells, but also tegument proteins that enable the virus to counteract cellular defense mechanisms immediately upon entering cells. The UL25 gene family of CMVs encodes such tegument proteins and also gives rise to related nonstructural proteins expressed early in infection...

Following spillover, viruses must adapt to new selection pressures exerted by antiviral responses in their new hosts. In mammals, cellular defense mechanisms often include viral nucleic acid editing pathways mediated through protein families apolipoprotein-B mRNA-editing complex (APOBEC) and Adenosine Deaminase Acting on ribonucleic acid (ADAR). APOBECs induce C→U transitions in viral genomes; the APOBEC locus is highly polymorphic with variable numbers of APOBEC3 paralogs and target preferences in humans and other mammals...

Hepatitis C virus (HCV) is a hepatotropic virus that establishes a chronic infection in most individuals. Effective treatments are available; however, many patients are not aware of their infection. Consequently, they do not receive treatment and HCV transmission remains high, particularly among groups at high risk of exposure such as people who inject intravenous drugs. A prophylactic vaccine may reduce HCV transmission, but is currently not available. HCV has evolved immune evasion strategies, which facilitate persistence and complicate development of a protective vaccine...

Inspite of the available antiviral therapy, hepatitis C virus (HCV) remains a global health burden and a prophylactic vaccine would help to eliminate the risk to develop chronic liver diseases. Structural insights into the function of the glycoproteins E1 and E2 in virus entry and the interplay with the host's humoral immune response are key for informed vaccine development. We review recently reported structural insights into receptor binding of HCV glycoproteins and the assembly of an intact membrane-bound E1-E2 heterodimer...

Influenza A viruses (IAVs) originating from animal reservoirs pose continuous threats to human health as demonstrated by the Spanish flu pandemic. Infection starts by attachment to host receptors, a crucial step that is targeted by immunological, prophylactic, and therapeutic intervention. Fine-tuning of virus hemagglutinin binding to host-specific receptor repertoires needs to remain balanced to receptor-destroying neuraminidase (NA) activity and is a key step in host adaptation. It determines NA-dependent virus motility, enabling IAVs to traverse the mucus layer and to bind to, and migrate over, the epithelial cell surface for reaching a location supporting endocytic uptake...

In the last few decades, several mosquito-borne arboviruses of zoonotic origin have established large-scale epidemic transmission cycles in the human population. It is often considered that arbovirus emergence is driven by adaptive evolution, such as virus adaptation for transmission by 'domestic' mosquito vector species that live in close association with humans. Here, I argue that although arbovirus adaptation to domestic mosquito vectors has been observed for several emerging arboviruses, it was generally not directly responsible for their initial emergence...

Many flaviviruses are well-known pathogens, such as dengue, Zika, Japanese encephalitis, and yellow fever viruses. Among them, dengue viruses cause global epidemics and threaten billions of people. Effective vaccines and antivirals are in desperate need. In this review, we focus on the recent advances in understanding viral nonstructural (NS) proteins as antiviral drug targets. We briefly summarize the experimental structures and predicted models of flaviviral NS proteins and their functions. We highlight a few well-characterized inhibitors targeting these NS proteins and provide an update about the latest development...

Acute hyperinflammatory virus infections, such as influenza or coronavirus disease-19, are still a major health burden worldwide. In these diseases, a massive overproduction of pro-inflammatory cytokines and chemokines (cytokine storm syndrome) determine the severity of the disease, especially in late stages. Direct-acting antivirals against these pathogens have to be administered very early after infection to be effective and may induce viral resistance. Here, we summarize data on a host-targeted strategy using inhibitors of the cellular Raf/MEK/ERK kinase cascade that not only block replication of different RNA viruses but also suppress the hyperinflammatory cytokine response upon infection...

Despite decades of suppressive antiretroviral therapy, human immunodeficiency virus (HIV) reservoirs in infected individuals persist and fuel viral rebound once therapy is interrupted. The persistence of viral reservoirs is the main obstacle to achieving HIV eradication or a long-term remission. The last decade has seen a profound change in our understanding of the mechanisms behind HIV persistence, which appears to be much more complex than originally assumed. In addition to the persistence of transcriptionally silent proviruses in a stable latent reservoir that is invisible to the immune system, HIV is increasingly recognized to persist by resistance to the immune clearance, which appears to play a surprisingly prominent role in shaping the reservoir...

Viral RNAs (vRNAs) are decorated by post-transcriptional modifications, including methylation of nucleotides. Methylations regulate biological functions linked to the sequence, structure, and protein interactome of RNA. Several RNA viruses were found to harbor 2'-O-methylations, affecting the ribose moiety of RNA. This mark was initially shown to target the first and second nucleotides of the 5'-end cap structure of mRNA. More recently, nucleotides within vRNA were also reported to carry 2'-O-methylations. The consequences of such methylations are still puzzling since they were associated with both proviral and antiviral effects...

While receptor binding is well recognized as a factor in influenza-A virus (IAV) and coronavirus (CoV) host adaptation, the role of viral glycoprotein cleavage has not been studied in detail so far. Interestingly, recent studies suggest that host species may differ in their protease repertoire available for cleavage. Furthermore, it was shown for certain bat-derived CoVs that proteolytic activation provides a critical barrier to infect human cells. Understanding the role of glycoprotein cleavage in different species and how IAV and CoVs adapt to a new protease repertoire may allow evaluating the zoonotic potential and risk posed by these viruses...

No abstract text is available yet for this article.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematologic malignancy linked to HTLV-1 infection, which is refractory to therapy. The precise mechanism of oncogenesis in ATLL is incompletely understood, however, oncogenic viral genes Tax and Hbz are implicated, and recent large genomic and transcriptome studies provide further insight. Despite progress in understanding the disease, survival and outcome with current therapies remain poor. Long-term survivors are reported, primarily among those with indolent disease or activating CC chemokine receptor 4 mutations, however, allogeneic hematopoietic stem cell transplant is the only curative treatment option...

The capacity of host cells to detect and restrict an infecting virus rests on an array of cell-autonomous antiviral effectors and innate immune receptors that can trigger inflammatory processes at tissue and organismal levels. Dynamic changes in protein abundance, subcellular localisation, post-translational modifications and interactions with other biomolecules govern these processes. Proteomics is therefore an ideal experimental tool to discover novel mechanisms of host antiviral immunity. Additional information can be gleaned both about host and virus by systematic analysis of viral immune evasion strategies...

Multi-drug-resistant bacteria are associated with significantly higher morbidity and mortality. The possibilities for discovering new antibiotics are limited, but phage therapy - the use of bacteriophages (viruses infecting bacteria) to cure infections - is now being investigated as an alternative or complementary treatment to antibiotics. However, one of the major limitations of this approach lies in the antagonistic coevolution between bacteria and bacteriophages, which determines the ultimate success or failure of phage therapy...

Global metagenomic surveys have revealed that bats host a diverse array of paramyxoviruses, including species from at least five major genera. An essential determinant of successful spillover is the entry of a virus into a new host. We evaluate the role of receptor usage in the zoonotic potential of bat-borne henipaviruses, morbilliviruses, pararubulaviruses, orthorubulaviruses, and jeilongviruses; successful spillover into humans depends upon compatibility of a respective viral attachment protein with its cognate receptor...