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1.  A virocentric perspective on the evolution of life 
Current opinion in virology  2013;3(5):546-557.
Viruses and/or virus-like selfish elements are associated with all cellular life forms and are the most abundant biological entities on Earth, with the number of virus particles in many environments exceeding the number of cells by one to two orders of magnitude. The genetic diversity of viruses is commensurately enormous and might substantially exceed the diversity of cellular organisms. Unlike cellular organisms with their uniform replication-expression scheme, viruses possess either RNA or DNA genomes and exploit all conceivable replication-expression strategies. Although viruses extensively exchange genes with their hosts, there exists a set of viral hallmark genes that are shared by extremely diverse groups of viruses to the exclusion of cellular life forms. Coevolution of viruses and host defense systems is a key aspect in the evolution of both viruses and cells, and viral genes are often recruited for cellular functions. Together with the fundamental inevitability of the emergence of genomic parasites in any evolving replicator system, these multiple lines of evidence reveal the central role of viruses in the entire evolution of life.
PMCID: PMC4326007  PMID: 23850169
2.  [No title available] 
PMCID: PMC3951680  PMID: 24525291
3.  [No title available] 
PMCID: PMC4077273  PMID: 24525288
4.  The Search for Meaning in Virus Discovery 
Current opinion in virology  2011;1(6):620-623.
PMCID: PMC4310690  PMID: 22440920
5.  Viral surveillance and discovery 
Current opinion in virology  2013;3(2):199-204.
The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health.
PMCID: PMC4310698  PMID: 23602435
6.  Editorial overview: virus–glycan interactions and pathogenesis 
PMCID: PMC4256938  PMID: 25128970
7.  Structural basis of glycan interaction in gastroenteric viral pathogens 
Current opinion in virology  2014;7:119-127.
A critical event in the life cycle of a virus is its initial attachment to host cells. This involves recognition by the viruses of specific receptors on the cell surface, including glycans. Viruses typically exhibit strain-dependent variations in recognizing specific glycan receptors, a feature that contributes significantly to cell tropism, host specificity, host adaptation and interspecies transmission. Examples include influenza viruses, noroviruses, rotaviruses, and parvoviruses. Both rotaviruses and noroviruses are well known gastroenteric pathogens that are of significant global health concern. While rotaviruses, in the family Reoviridae, are the major causative agents of life-threatening diarrhea in children, noroviruses, which belong to Caliciviridae family, cause epidemic and sporadic cases of acute gastroenteritis across all age groups. Both exhibit enormous genotypic and serotypic diversity. Consistent with this diversity each exhibits strain-dependent variations in the types of glycans they recognize for cell attachment. This chapter reviews current status of the structural biology of such strain-dependent glycan specificities in these two families of viruses.
PMCID: PMC4251800  PMID: 25073118
8.  Evolution of different antiviral strategies in wild mouse populations exposed to different gammaretroviruses 
Current opinion in virology  2013;3(6):10.1016/j.coviro.2013.08.001.
Laboratory mice carry 3 host range groups of gammaretroviruses all of which are linked to leukemia induction. Although polytropic mouse leukemia viruses (P-MLVs) are generally recognized as the proximate cause of MLV-induced leukemias in laboratory mice, wild mice that carry only endogenous P-MLVs do not produce infectious virus and are not prone to disease; these mice carry the permissive XPR1 retroviral receptor and an attenuated variant of the retroviral restriction factor, APOBEC3. In contrast, Eurasian mice carrying ecotropic and xenotropic MLVs have evolved multiple restrictive XPR1 variants, other factors that interfere with MLV entry, and more effectively antiviral variants of APOBEC3. These different antiviral restrictions in Mus musculus subspecies suggest that the different virus types found in these natural populations may pose different but largely uncharacterized survival risks in their host subspecies.
PMCID: PMC3855896  PMID: 23992668
mouse gammaretroviruses; XPR1 retrovirus receptor; retrovirus restriction; mouse APOBEC3
9.  HIV Accessory Proteins versus Host Restriction Factors 
Current opinion in virology  2013;3(6):10.1016/j.coviro.2013.08.004.
Primate immunodeficiency viruses, including HIV-1, are characterized by the presence of accessory genes such as vif, vpr, vpx, vpu, and nef. Current knowledge indicates that none of the primate lentiviral accessory proteins has enzymatic activity. Instead, these proteins interact with cellular ligands to either act as adapter molecules to redirect the normal function of host factors for virus-specific purposes or to inhibit a normal host function by mediating degradation or causing intracellular mislocalization/sequestration of the factors involved. This review aims at providing an update of our current understanding of how Vif, Vpu, and Vpx control the cellular restriction factors APOBEC3G, BST-2, and SAMHD1, respectively.
PMCID: PMC3855913  PMID: 24246762
10.  Avian Retroviral Replication 
Current opinion in virology  2013;3(6):10.1016/j.coviro.2013.08.008.
Avian retroviruses have undergone intense study since the beginning of the 20th century. They were originally identified as cancer-inducing filterable agents in chicken neoplasms. Since their discovery, the study of these simple retroviruses has contributed greatly to our understanding of retroviral replication and cancer. Avian retroviruses are continuing to evolve and have great economic importance in the poultry industry worldwide. The aim of this review is to provide a broad overview of the genome, pathology, and replication of avian retroviruses. Notable gaps in our current knowledge are highlighted, and areas where avian retroviruses differ from other retrovirus are also emphasized.
PMCID: PMC3875226  PMID: 24011707
11.  Alu elements: An intrinsic source of human genome instability 
Current opinion in virology  2013;3(6):639-645.
Alu elements are ~300 bp sequences that have amplified via an RNA intermediate leading to the accumulation of over 1 million copies in the human genome. Although few of the copies are active, Alu germline activity is the highest of all human retrotransposons and does significantly contribute to genetic disease and population diversity. There are two basic mechanisms by which Alu elements contribute to disease: through insertional mutagenesis and as a large source of repetitive sequences that contribute to non-allelic homologous recombination that cause genetic deletions and duplications.
PMCID: PMC3982648  PMID: 24080407
12.  HIV-1 Entry Inhibitors: Recent Development and Clinical Use 
Current opinion in virology  2013;3(1):51-57.
Purpose of review
This review provides an overview of HIV-1 entry inhibitors, with a focus on drugs in the later stages of clinical development.
Recent findings
Entry of HIV-1 into target cells involves viral attachment, co-receptor binding and fusion. Antiretroviral drugs that interact with each step in the entry process have been developed, but only two are currently approved for clinical use. The small molecule attachment inhibitor BMS-663068 has shown potent antiviral activity in early phase studies, and phase 2b trials are currently underway. The post-attachment inhibitor ibalizumab has shown antiviral activity in phase 1 and 2 trials; further studies, including subcutaneous delivery of drug to healthy individuals, are anticipated. The CCR5 antagonist maraviroc is approved for use in treatment-naïve and treatment-experienced patients. Cenicriviroc, a small-molecule CCR5 antagonist that also has activity as a CCR2 antagonist, has entered phase 2b studies. No CXCR4 antagonists are currently in clinical trials, but once daily, next-generation injectable peptide fusion inhibitors have entered human trials. Both maraviroc and ibalizumab are being studied for prevention of HIV-1 transmission and/or for use in nucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens.
Inhibition of HIV-1 entry continues to be a promising target for antiretroviral drug development.
PMCID: PMC4213740  PMID: 23290628
attachment inhibitors; chemokine receptor antagonist; fusion inhibitor; HIV-1 envelope
13.  Editorial overview: Virus structure and function 
Current opinion in virology  2014;5:viii-ix.
PMCID: PMC4209247  PMID: 24726158
14.  Impact of host and virus genome variability on HCV replication and response to interferon 
Current opinion in virology  2013;3(5):501-507.
Since the discovery of hepatitis C virus (HCV), treatment has proven difficult and the regimen of pegylated interferon-α and ribavirin is only effective for half of patients. Evidence suggests that host and viral genome variations play a role in either viral clearance or persistence. Powerful genomic technologies have made it possible to study genome-wide associations with treatment response, which yielded critical genetic polymorphisms that predict treatment response. This has important implications for treatment of HCV infection and opened the door to the possibility of genetic marker-guided treatment (personalized medicine). This review will focus on the recent advances in understanding host and viral genetic variations with regards to treatment and the importance for future therapeutic intervention.
PMCID: PMC3797205  PMID: 23835049
15.  Influenza virus hemagglutinin stalk-based antibodies and vaccines 
Current opinion in virology  2013;3(5):521-530.
Antibodies against the conserved stalk domain of the hemagglutinin are currently being discussed as promising therapeutic tools against influenza virus infections. Due to the conservation of the stalk domain these antibodies are able to broadly neutralize a wide spectrum of influenza virus strains and subtypes. Broadly protective vaccine candidates based on the epitopes of these antibodies, e.g. chimeric and headless hemagglutinin structures, are currently under development and show promising results in animals models. These candidates could be developed into universal influenza virus vaccines that protect from infection with drifted seasonal as well as novel pandemic influenza virus strains therefore obviating the need for annual vaccination, and enhancing our pandemic preparedness.
PMCID: PMC3804342  PMID: 23978327
16.  Recent Trends in HIV-1 Drug Resistance 
Current opinion in virology  2013;3(5):487-494.
Once considered an inevitable consequence of HIV treatment, drug resistance is declining. This decline supports the hypothesis that antiretroviral therapy can arrest replication and prevent the evolution of resistance. Further support comes from excellent clinical outcomes, the failure of treatment intensification to reduce residual viremia, the lack of viral evolution in patients on optimal therapy, pharmacodynamics studies explaining the extraordinarily high antiviral activity of modern regimens, and recent reports of potential cures. Evidence supporting ongoing replication includes higher rates of certain complications in treated patients and an increase in circular forms of the viral genome after intensification with integrase inhibitors. Recent studies also provide an explanation for the observation that some patients fail protease-inhibitor based regimens without evidence for resistance.
PMCID: PMC3963152  PMID: 24021560
17.  Host genetic determinants of influenza pathogenicity 
Current opinion in virology  2013;3(5):531-536.
Despite effective vaccines, influenza remains a major global health threat due to the morbidity and mortality caused by seasonal epidemics, as well as the 2009 pandemic. Also of profound concern are the rare but potentially catastrophic transmissions of avian influenza to humans, highlighted by a recent H7N9 influenza outbreak. Murine and human studies reveal that the clinical course of influenza is the result of a combination of both host and viral genetic determinants. While viral pathogenicity has long been the subject of intensive efforts, research to elucidate host genetic determinants, particularly human, is now in the ascendant, and the goal of this review is to highlight these recent insights.
PMCID: PMC4127448  PMID: 23933004
18.  The genetics of host–virus coevolution in invertebrates 
•No genetic data are available on viruses or antiviral defence for most animal phyla.•The research bias may bias understanding of host–virus coevolution.•Antiviral RNAi genes of Drosophila display rapid adaptive evolution.•There is no difference between plant, vertebrate, and insect viruses in median dN/dS ratio.•High-frequency large-effect segregating polymorphisms provide evidence for coevolution.
Although viral infection and antiviral defence are ubiquitous, genetic data are currently unavailable from the vast majority of animal phyla — potentially biasing our overall perspective of the coevolutionary process. Rapid adaptive evolution is seen in some insect antiviral genes, consistent with invertebrate-virus ‘arms-race’ coevolution, but equivalent signatures of selection are hard to detect in viruses. We find that, despite the large differences in vertebrate, invertebrate, and plant immune responses, comparison of viral evolution fails to identify any difference among these hosts in the impact of positive selection. The best evidence for invertebrate-virus coevolution is currently provided by large-effect polymorphisms for host resistance and/or viral evasion, as these often appear to have arisen and spread recently, and can be favoured by virus-mediated selection.
PMCID: PMC4199324  PMID: 25063907
19.  The role of viral evolution in rabies host shifts and emergence 
•Rabies virus has a broad host range, but transmission cycles are species-specific.•Significant barriers limit viral establishment in new host species, but are poorly characterised.•Viral preadaptation may facilitate emergence, but does not rule out host adaptation.•Several lines of evidence point to adaptation of Rabies virus to specific hosts.
Despite its ability to infect all mammals, Rabies virus persists in numerous species-specific cycles that rarely sustain transmission in alternative species. The determinants of these species-associations and the adaptive significance of genetic divergence between host-associated viruses are poorly understood. One explanation is that epidemiological separation between reservoirs causes neutral genetic differentiation. Indeed, recent studies attributed host shifts to ecological factors and selection of ‘preadapted’ viral variants from the existing viral community. However, phenotypic differences between isolates and broad scale comparative and molecular evolutionary analyses indicate multiple barriers that Rabies virus must overcome through adaptation. This review assesses various lines of evidence and proposes a synthetic hypothesis for the respective roles of ecology and evolution in Rabies virus host shifts.
PMCID: PMC4199325  PMID: 25064563
20.  The polymerase of negative-stranded RNA viruses 
Current opinion in virology  2013;3(2):103-110.
Negative-sense (NS) RNA viruses deliver into cells a mega-dalton RNA-protein complex competent for transcription. Within this complex, the RNA is protected in a nucleocapsid protein (NP) sheath which the viral polymerase negotiates during RNA synthesis. The NP-RNA templates come as nonsegemented (NNS) or segmented (SNS), necessitating distinct strategies for transcription by their polymerases. Atomic-level understanding of the NP-RNA of both NNS and SNS RNA viruses show that the RNA must be transiently dissociated from NP during RNA synthesis. Here we summarize and compare the polymerases of NNS and SNS RNA viruses, and the current structural data on the polymerases. Those comparisons inform us on the evolution of related RNA synthesis machines which use two distinct mechanisms for mRNA cap formation.
PMCID: PMC4159711  PMID: 23602472
21.  T-cell Immunity to Human Alphaherpesviruses 
Current opinion in virology  2013;3(4):452-460.
Human alphaherpesviruses (αHHV) – herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus – infect mucosal epithelial cells, establish a lifelong latent infection of sensory neurons, and reactivate intermittingly to cause recrudescent disease. Although chronic αHHV infections co-exist with brisk T-cell responses, T-cell immune suppression is associated with worsened recurrent infection. Induction of αHHV-specific T-cell immunity is complex and results in poly-specific CD4 and CD8 T-cell responses in peripheral blood. Specific T-cells are localized to ganglia during the chronic phase of HSV infection and to several infected areas during recurrences, and persist long after viral clearance. These recent advances hold promise in the design of new vaccine candidates.
PMCID: PMC3748210  PMID: 23664660
22.  Functional genomics approaches to understand cytomegalovirus replication, latency and pathogenesis 
Current opinion in virology  2013;3(4):408-415.
Cytomegalovirus (CMV) is a species-specific herpesvirus that is ubiquitous in the population and has the potential to cause significant disease in immunocompromised individuals as well as in congenitally infected infants. CMV establishes latency in cells of the myeloid lineage following primary infection. High-throughput functional genomics approaches have provided insight into the mechanisms of CMV replication, but although CMV latency cell models have been useful in elucidating the mechanisms of viral latency and reactivation, omics approaches have proven challenging in these cell systems. This review will summarize the current state of knowledge concerning the use of functional genomics technologies to understand mechanisms of CMV replication, latency and pathogenesis.
PMCID: PMC3748260  PMID: 23816389
23.  Interrogating the relationship between naïve and immune antiviral T cell repertoires 
Current opinion in virology  2013;3(4):447-451.
Understanding how naïve virus-specific CD8+ T cells influence the type of immune response generated after virus infection is critical for the development of enhanced therapeutic and vaccination strategies to exploit CD8+ T cell-mediated immunity. Recent technological advances in T cell isolation and T receptor sequencing have allowed for greater understanding of the basic structure of immune T cell repertoires, the diversity of responses within and between individuals, and changes in repertoires over time and in response to infection conditions. In this review, we discuss the current understanding of how T cell repertoires contribute to potent antiviral responses. Additionally we compare the state of the art in receptor sequencing, highlighting the advantages and disadvantages of the three most common approaches: next-generation sequencing, template-switch anchored RT-PCR, and multiplex single cell PCR. Finally, we describe how TCR sequencing has delineated the relationship between naïve and immune T cell repertoires.
PMCID: PMC3779657  PMID: 23849601
24.  Role of T cell immunity in recovery from influenza virus infection 
Current opinion in virology  2013;3(4):425-429.
Influenza virus infection has the potential to induce excess pulmonary inflammation and massive tissue damage in the infected host. Conventional CD4+ and CD8+ as well as nonconventional innate like T cells respond to infection and make an essential contribution to the clearance of virus infected cells and the resolution of pulmonary inflammation and injury. Emerging evidence in recent years has suggested a critical role of local interactions between lung effector T cells and antigen presenting cells in guiding the accumulation, differentiation and function of effector T cells beyond their initial activation in the draining lymph nodes during influenza infection. As such, lung effector CD4+ and CD8+ T cells utilize multiple effector and regulatory mechanisms to eliminate virus infected cells as well as fine tune the control of pulmonary inflammation and injury. Elucidating the mechanisms by which conventional and nonconventional T cells orchestrate their response in the lung as well as defining the downstream events required for the resolution of influenza infection will be important areas of future basic research which in turn may result in new therapeutic strategies to control the severity of influenza virus infection.
PMCID: PMC3804899  PMID: 23721865
25.  Insights into chronic gamma-herpesvirus infections 
Current opinion in virology  2013;3(3):225-226.
PMCID: PMC4118582  PMID: 23743126

Results 1-25 (135)