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Current Opinion in Virology

Fadila Amraoui, Anna-Bella Failloux
Since the first outbreak of chikungunya in Italy in 2007, Europe has been facing an increase in local transmission of arboviral diseases. Dengue virus (DENV) and chikungunya virus (CHIKV) are both transmitted by the mosquito Aedes albopictus present in 20 European countries. CHIKV emergence in Europe was mainly associated with the East-Central-South African (ECSA) genotype, recently exemplified by the 11 CHIKV cases in southern France in 2014. Despite hundreds of travelers returning from the Americas where the Asian CHIKV genotype was responsible for more than one million cases, no autochthonous transmission associated with the Asian genotype was reported in Europe...
October 19, 2016: Current Opinion in Virology
Sineewanlaya Wichit, Pauline Ferraris, Valérie Choumet, Dorothée Missé
Arboviruses such as Dengue, Chikungunya, and Zika viruses represent a major public health problem due to globalization and propagation of susceptible vectors worldwide. Arthropod vector-derived salivary factors have the capacity to modulate human cells function by enhancing or suppressing viral replication and, therefore, modify the establishment of local and systemic viral infection. Here, we discuss how mosquito saliva may interfere with Dengue virus (DENV) infection in humans. Identification of saliva factors that enhance infectivity will allow the production of vector-based vaccines and therapeutics that would interfere with viral transmission by targeting arthropod saliva components...
October 19, 2016: Current Opinion in Virology
Karla Kirkegaard, Nicholas J van Buuren, Roberto Mateo
If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections, newly synthesized viral genomes occupy the same cells as parent and other progeny genomes. If the antiviral target is chosen so that the drug-resistant progeny's growth is dominantly inhibited by the drug-susceptible members of its intracellular family, its outgrowth can be suppressed. Precedent for 'dominant drug targeting' as a deliberate approach to suppress the outgrowth of inhibitor-resistant viruses has been established for envelope variants of vesicular stomatitis virus and for capsid variants of poliovirus and dengue virus...
October 17, 2016: Current Opinion in Virology
Simonetta Bandiera, C Billie Bian, Yujin Hoshida, Thomas F Baumert, Mirjam B Zeisel
Hepatitis C virus (HCV) infection is one of the major causes of advanced liver disease and hepatocellular carcinoma (HCC) worldwide. While the knowledge about the molecular virology of HCV infection has markedly advanced, the molecular mechanisms of disease progression leading to fibrosis, cirrhosis and HCC are still unclear. Accumulating experimental and clinical studies indicate that HCV may drive hepatocarcinogenesis directly via its proteins or transcripts, and/or indirectly through induction of chronic liver inflammation...
October 11, 2016: Current Opinion in Virology
Joana Rocha-Pereira, Jana Van Dycke, Johan Neyts
Human noroviruses are the leading cause of foodborne illness causing both acute and chronic gastroenteritis. In recent years, a number of vaccine candidates entered (pre-) clinical development and the first efforts to develop antiviral therapy have been made. We here discuss aspects of norovirus genetic evolution, persistence in immunocompromised patients as well as the risk and potential consequences of resistance development toward future antiviral drugs.
October 10, 2016: Current Opinion in Virology
Frank Buchholz, Joachim Hauber
Chronic viral infections are often incurable because current antiviral strategies do not target chromosomally integrated or non-replicating episomal viral genomes. The rapid development of technologies for genome editing may possibly soon allow for therapeutic targeting of viral genomes and, hence, for development of curative strategies for persistent viral infection. However, detailed investigation of different antiviral genome editing approaches recently revealed various undesired effects. In particular, the problem of frequent and swift development of resistant viruses has to be thoroughly analysed before genome editing approaches become an established option for antiviral treatment...
October 7, 2016: Current Opinion in Virology
Walter J Tabachnick
Mosquitoes transmit many viruses to a variety of hosts. Cycles of mosquito borne arbovirus transmission are the result of complex interactions between the mosquito, the arbovirus and the host that are influenced by genetic variations in a variety of traits in each that are all influenced by many environmental factors. R0, the basic reproduction number or mean number of individuals infected from a single infected individual, is a measure of mosquito borne arbovirus transmission. Understanding the causes for the distribution of R0 in any transmission cycle is a daunting challenge due to the lack of information on the genetic and environmental variances that influence R0...
September 28, 2016: Current Opinion in Virology
Ann M Moormann, Jeffrey A Bailey
Burkitt lymphoma (BL) is >90% EBV-associated when this pediatric cancer is diagnosed in regions heavily burden by endemic Plasmodium falciparum malaria and thus has been geographically classified as endemic BL. The incidence of endemic BL is 10-fold higher compared to BL diagnosed in non-malarious regions of the world. The other forms of BL have been classified as sporadic BL which contain EBV in ∼30% of cases and immunodeficiency BL which occurs in HIV-infected adults with ∼40% of tumors containing EBV...
September 26, 2016: Current Opinion in Virology
Jennifer Totonchy, Ethel Cesarman
Non-Hodgkin lymphomas are highly increased in incidence in individuals infected with HIV, and this continues to be the case in spite of highly effective combined antiretroviral therapy (cART). New evidence has demonstrated that while successful virtual recovery of CD4 counts and elimination of HIV from peripheral blood can be achieved with cART, viral replication can still occur in lymphoid tissues. In addition, recent studies have suggested that adipose tissue provides an additional reservoir for HIV-infected macrophages and T lymphocytes even in the context of successful cART therapy...
September 22, 2016: Current Opinion in Virology
Nelson Martins, Jean-Luc Imler, Carine Meignin
Developing antiviral drugs is challenging due to the small number of targets in viruses, and the rapid evolution of viral genes. Animals have evolved a number of efficient antiviral defence mechanisms, which can serve as a source of inspiration for novel therapies. The genetically tractable insect Drosophila belongs to the most diverse group of animals. Genetic and transcriptomic analyses have recently identified Drosophila genes encoding viral restriction factors. Some of them represent evolutionary novelties and their characterization may provide hints for the design of directly acting antivirals...
September 19, 2016: Current Opinion in Virology
Brian G Pierce, Zhen-Yong Keck, Steven Kh Foung
Hepatitis C virus (HCV) is a major global disease burden, often leading to chronic liver diseases, cirrhosis, cancer, and death in those infected. Despite the recent approval of antiviral therapeutics, a preventative vaccine is recognized as the most effective means to control HCV globally, particularly in at-risk and developing country populations. Here we describe the efforts and challenges related to the development of an HCV vaccine, which after decades of research have not been successful. Viral sequence variability poses a major challenge, yet recent research has provided unprecedented views of the atomic structure of HCV epitopes and immune recognition by antibodies and T cell receptors...
September 19, 2016: Current Opinion in Virology
Eliana G Acosta, Ralf Bartenschlager
Dengue virus (DENV) is a human threat of increasing importance. Although a tetravalent vaccine has been recently approved, owing to limited efficacy there is still an urgent need for antiviral drugs to prevent or treat DENV infections. Traditionally, antiviral drug discovery has focused on molecules targeting viral factors. However, thus far the identification of direct-acting antiviral drugs with potent DENV pan-serotypic activity has been problematic. An alternative are host-targeting antiviral drugs that hold great promise for broad-spectrum activity...
September 17, 2016: Current Opinion in Virology
Kerry E Mauck
Virus infection can elicit changes in host plant cues that mediate vector orientation, feeding, and dispersal. Given the importance of plant cues for vector-mediated virus transmission, it is unlikely that selection is blind to these effects. Indeed, there are many examples of viruses altering plant cues in ways that should enhance transmission. However, there are also examples of viruses inducing transmission-limiting plant phenotypes. These apparently mal-adaptive effects occur when viruses experience host plant environments that also limit infectivity or within-host multiplication...
September 16, 2016: Current Opinion in Virology
Svetlana Atasheva, Dmitry M Shayakhmetov
The host immune system developed multiple ways for recognition of viral pathogens. Upon disseminated adenovirus infection, the immune system senses adenovirus invasion from the moment it enters the bloodstream. The soluble blood factors, FX, antibodies, and complement, can bind and activate plethora of host-protective immune responses. Adenovirus binding to the cellular β3 integrin and endosomal membrane rupture trigger activation of IL-1α/IL-1R1 proinflammatory cascade leading to attraction of cytotoxic immune cells to the site of infection...
September 14, 2016: Current Opinion in Virology
Chiara Borsotti, Ester Borroni, Antonia Follenzi
Lentiviral vectors (LVs)-mediated gene transfer is an efficient method for ex vivo and in vivo gene therapy. Actually, LVs have been used in several clinical trials and therapeutic correction was reached in affected patients. However, in order to be effective gene therapy needs to be efficient without detrimental effects for target cells. Successful cell transduction by LVs can be hampered by several factors such as the activation of innate immune sensors during cell transduction and different restriction factors (RFs) inhibiting viral replication inside the cells...
September 13, 2016: Current Opinion in Virology
William F Goins, Bonnie Hall, Justus B Cohen, Joseph C Glorioso
Gene therapy applications depend on vector delivery and gene expression in the appropriate target cell. Vector infection relies on the distribution of natural virus receptors that may either not be present on the desired target cell or distributed in a manner to give off-target gene expression. Some viruses display a very limited host range, while others, including herpes simplex virus (HSV), can infect almost every cell within the human body. It is often an advantage to retarget virus infectivity to achieve selective target cell infection...
September 7, 2016: Current Opinion in Virology
Christian Kranjec, John Doorbar
The aetiologic association between infection with certain human papillomavirus (HPV) types, high-grade squamous neoplasia, and cancer at different epithelial sites is well established. In this review we briefly discuss recent breakthroughs in the regulation of squamous epithelia in homeostasis and disease, and provide a view of how these discoveries modify our understanding of how HPV-induced neoplasia in squamous epithelia is triggered. Taken together, these observations highlight how HPVs have evolved the ability to inactivate the products of genes that are frequently mutated in non-HPV-associated pre-neoplasia and squamous cell carcinoma of sun-exposed skin, and introduce a Darwinian model of clonal evolution of HPV-infected cells...
September 3, 2016: Current Opinion in Virology
Arun Srivastava
In this review, a brief account of the historical perspective of the discovery of the first cellular receptor and co-receptor of the prototype adeno-associated virus serotype 2 (AAV2) will be presented. The Subsequent discovery of a number of AAV serotypes, and attempts to identify the cellular receptors and co-receptors for these serotype vectors has had significant implications in their use in human gene therapy. As additional AAV serotypes are discovered and isolated, a detailed understanding of their tropism is certainly likely to play a key role in all future studies, both basic science as well as clinical...
September 2, 2016: Current Opinion in Virology
Amanda R Panfil, Michael P Martinez, Lee Ratner, Patrick L Green
Human T-cell leukemia virus type 1 (HTLV-1) is a tumorigenic delta retrovirus and the causative infectious agent of a non-Hodgkin's peripheral T-cell malignancy called adult T-cell leukemia/lymphoma (ATL). ATL develops in approximately 5% of infected individuals after a significant clinical latency period of several decades. Clinical classifications of ATL include smoldering, chronic, lymphoma, and acute subtypes, with varying median survival ranges of a few months to several years. Depending on the ATL subtype and disease symptoms, treatment options include 'watchful waiting', chemotherapy, antiviral therapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and targeted therapies...
August 31, 2016: Current Opinion in Virology
Christian Münz
Epstein Barr virus (EBV) is a human γ-herpesvirus that was discovered in Burkitt's lymphoma more than 50 years ago. Since then it has been proposed as the causative agent of up to 2% of all tumors worldwide, mainly lymphomas and epithelial cell carcinomas. Surprisingly, persistent EBV infection is at the same time found in more than 90% of healthy human adults. Even the very same programs of EBV infection that are found in the associated malignancies are continuously present in healthy EBV carriers. We will discuss primary immunodeficiencies and immune compartment changes during the first decade of human life that give us insights into how tumorigenesis by persistent EBV infection and Hodgkin's lymphoma predisposing infectious mononucleosis is prevented during primary infection...
August 31, 2016: Current Opinion in Virology
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