authoritative, comprehensive and systematic

Viral modulation of programmed necrosis

Vaccines for viral hemorrhagic fevers—progress and shortcomings

Antiviral options for biodefense

Kaposi sarcoma associated herpesvirus pathogenesis (KSHV)—an update

Poliovirus vaccination options for achieving eradication and securing the endgame

Using epigenetics to define vaccine-induced memory T cells

Challenges in the clinical development of a dengue vaccine

Rhesus macaque rhadinovirus-associated disease

The role of T cell immunity in HIV-1 infection

?-Herpesvirus-encoded miRNAs and their roles in viral biology and pathogenesis

Metagenomics and future perspectives in virus discovery

Monitoring the emergence and re-emergence of viral diseases with the goal of containing the spread of viral agents requires both adequate preparedness and quick response. Identifying the causative agent of a new epidemic is one of the most important steps for effective response to disease outbreaks. Traditionally, virus discovery required propagation of the virus in cell culture, a proven technique responsible for the identification of the vast majority of viruses known to date. However, many…

Volume 2, Issue 1, 01 February 2012, Pp 63-77
Mokili, J.L. | Rohwer, F. | Dutilh, B.E.

Interferon-stimulated genes and their antiviral effector functions

Many viruses trigger the type I interferon (IFN) system, leading to the transcription of hundreds of interferon-stimulated genes (ISGs). The products of these ISGs exert numerous antiviral effector functions, many of which are still not fully described. Recent efforts have been aimed at identifying which ISGs are antiviral and further characterizing their mechanisms of action. IFN effectors vary widely in their magnitude of inhibitory activity and display combinatorial antiviral properties.…

Volume 1, Issue 6, 01 December 2011, Pp 519-525
Schoggins, J.W. | Rice, C.M.

RIG-I like receptors and their signaling crosstalk in the regulation of antiviral immunity

During virus infection, multiple immune signaling pathways are triggered, both within the host cell and bystander cells of an infected tissue. These pathways act in concert to mediate innate antiviral immunity and to initiate the inflammatory response against infection. The RIG-I-like receptor (RLR) family of pattern recognition receptors (PRRs) is a group of cytosolic RNA helicase proteins that can identify viral RNA as nonself via binding to pathogen associated molecular pattern (PAMP) motifs…

Volume 1, Issue 3, 01 September 2011, Pp 167-176
Ramos, H.J. | Gale Jr., M.

The role of receptor binding specificity in interspecies transmission of influenza viruses

Influenza A virus infection begins with the binding of the hemagglutinin (HA) glycoprotein to sialic acid-containing receptors on the surface of the target cell. Avian influenza viruses, including avian H5N1, H7, and H9N2 viruses, can occasionally cross the species barrier and infect humans; however, these viruses do not spread efficiently from person to person, perhaps, partly, owing to differences in the receptor-binding specificities of human and avian influenza viruses. The HAs of avian…

Volume 2, Issue 2, 01 April 2012, Pp 160-167
Imai, M. | Kawaoka, Y.

Antivirals and resistance: Influenza virus

Influenza causes annual epidemics of respiratory viral infections are associated with significant morbidity and mortality. Influenza vaccines have been shown to reduce the risk of infection and mitigate against some of the virus' sequellae. Likewise, two classes of antivirals, the adamantanes (amantadine and rimantadine) and the neuraminidase inhibitors (laninamivir, oseltamivir, peramivir, and zanamivir) are currently approved for the prevention and treatment of influenza; several other…

Volume 1, Issue 6, 01 December 2011, Pp 563-573
Ison, M.G.

Inborn errors of anti-viral interferon immunity in humans

The three types of interferon (IFNs) are essential for immunity against at least some viruses in the mouse model of experimental infections, type I IFNs displaying the broadest and strongest anti-viral activity. Consistently, human genetic studies have shown that type II IFN is largely redundant for immunity against viruses in the course of natural infections. The precise contributions of human type I and III IFNs remain undefined. However, various inborn errors of anti-viral IFN immunity have…

Volume 1, Issue 6, 01 December 2011, Pp 487-496
Sancho-Shimizu, V. | Perez De Diego, R. | Jouanguy, E. | Zhang, S.-Y. | Casanova, J.-L.

Paleovirology - Ghosts and gifts of viruses past

The emerging field of paleovirology aims to study the evolutionary age and impact of ancient viruses (paleoviruses) on host biology. Despite a historical emphasis on retroviruses, paleoviral 'fossils' have recently been uncovered from a broad swathe of viruses. These viral imprints have upended long-held notions of the age and mutation rate of viruses. While 'direct' paleovirology relies on the insertion of viral genes in animal genomes, examination of adaptive changes in host genes that…

Volume 1, Issue 4, 01 October 2011, Pp 304-309
Patel, M.R. | Emerman, M. | Malik, H.S.

Predicting 'airborne' influenza viruses: (Trans-) mission impossible?

Repeated transmission of animal influenza viruses to humans has prompted investigation of the viral, host, and environmental factors responsible for transmission via aerosols or respiratory droplets. How do we determine - out of thousands of influenza virus isolates collected in animal surveillance studies each year - which viruses have the potential to become 'airborne', and hence pose a pandemic threat? Here, using knowledge from pandemic, zoonotic and epidemic viruses, we postulate that the…

Volume 1, Issue 6, 01 December 2011, Pp 635-642
Sorrell, E.M. | Schrauwen, E.J.A. | Linster, M. | De Graaf, M. | Herfst, S. | Fouchier, R.A.M.

Broadly neutralizing antibodies against influenza virus and prospects for universal therapies

Vaccines are the gold standard for the control and prevention of infectious diseases, but a number of important human diseases remain challenging targets for vaccine development. An influenza vaccine that confers broad spectrum, long-term protection remains elusive. Several broadly neutralizing antibodies have been identified that protect against multiple subtypes of influenza A viruses, and crystal structures of several neutralizing antibodies in complex with the major influenza surface…

Volume 2, Issue 2, 01 April 2012, Pp 134-141
Ekiert, D.C. | Wilson, I.A.

Bacteriophages and their genomes

Bacteriophages occupy a unique position in biology, representing an absolute majority of all organisms in the biosphere. Because their genomes are relatively small, elucidating the genetic diversity of the phage population, deciphering their origins, and identifying the evolutionary mechanisms that shape the population would seem readily feasible. And yet the pace of phage genome characterization has slowed over the past three years, reflecting partly a need to transition from sequencing known…

Volume 1, Issue 4, 01 October 2011, Pp 298-303
Hatfull, G.F. | Hendrix, R.W.

Ultra-deep sequencing for the analysis of viral populations

Next-generation sequencing allows for cost-effective probing of virus populations at an unprecedented level of detail. The massively parallel sequencing approach can detect low-frequency mutations and it provides a snapshot of the entire virus population. However, analyzing ultra-deep sequencing data obtained from diverse virus populations is challenging because of PCR and sequencing errors and short read lengths, such that the experiment provides only indirect evidence of the underlying viral…

Volume 1, Issue 5, 01 November 2011, Pp 413-418
Beerenwinkel, N. | Zagordi, O.

Poxvirus host cell entry

Poxviruses are characterized by their large size, complex composition, and cytoplasmic life cycle. They produce two types of infectious particles: mature virions (MVs) and extracellular virions (EVs). Both MVs and EVs of vaccinia virus, the model poxvirus, take advantage of host cell endocytosis for internalization: they activate macropinocytosis - the most suitable form of endocytosis for large particles. Although largely dependent on the same cellular machinery, MV and EV entry differs with…

Volume 2, Issue 1, 01 February 2012, Pp 20-27
Schmidt, F.I. | Bleck, C.K.E. | Mercer, J.

Exploring the viral world through metagenomics

Viral metagenomics, or shotgun sequencing of purified viral particles, has revolutionized the field of environmental virology by allowing the exploration of viral communities in a variety of sample types throughout the biosphere. The introduction of viral metagenomics has demonstrated that dominant viruses in environmental communities are not well-represented by the cultured viruses in existing sequence databases. Viral metagenomic studies have provided insights into viral ecology by…

Volume 1, Issue 4, 01 October 2011, Pp 289-297
Rosario, K. | Breitbart, M.

Genotype constellation and evolution of group A rotaviruses infecting humans

Numerous rotavirus group A (RVA) strains with distinct G-genotype and P-genotype combinations have been described infecting humans worldwide. However, the increasing amount of complete RVA genome data which have become available, suggest that only RVA strains with 2 discrete genotype constellations have been successful in sustaining infection of humans worldwide over longer periods of time. Those genotype constellations have been designated I1-R1-C1-M1-A1-N1-T1- E1-H1 and…

Volume 2, Issue 4, 01 August 2012, Pp 426-433
Matthijnssens, J. | Van Ranst, M.

Mass extinctions, biodiversity and mitochondrial function: Are bats 'special' as reservoirs for emerging viruses?

For the past 10-15 years, bats have attracted growing attention as reservoirs of emerging zoonotic viruses. This has been due to a combination of factors including the emergence of highly virulent zoonotic pathogens, such as Hendra, Nipah, SARS and Ebola viruses, and the high rate of detection of a large number of previously unknown viral sequences in bat specimens. As bats have ancient evolutionary origins and are the only flying mammals, it has been hypothesized that some of their unique…

Volume 1, Issue 6, 01 December 2011, Pp 649-657
Wang, L.-F. | Walker, P.J. | Poon, L.L.M.

Herpesvirus capsid assembly: Insights from structural analysis

In all herpesviruses, the capsid is icosahedral in shape, composed of 162 capsomers, and assembled in the infected cell nucleus. Once a closed capsid is formed, it is packaged with the virus DNA and transported to the cytoplasm where further morphogenetic events take place. Herpesvirus capsid populations are highly uniform in shape, and this property has made them attractive for structural analysis particularly by cryo electron microscopy followed by three-dimensional image reconstruction. Here…

Volume 1, Issue 2, 01 August 2011, Pp 142-149
Brown, J.C. | Newcomb, W.W.

Hepatitis C virus host cell entry

The hepatitis C virus (HCV) is a major medical problem with at least 130 million infected individuals worldwide. Over the last decade multiple host factors required for HCV cell entry have been identified, but a detailed understanding of their mechanistic interplay remains elusive. Nonetheless, recent advances in defining species-specific barriers of HCV transmission have allowed the identification of a minimal set of entry factors that are required for HCV infection of rodent cells and has…

Volume 2, Issue 1, 01 February 2012, Pp 14-19
Ploss, A. | Evans, M.J.

3′ Cap-independent translation enhancers of positive-strand RNA plant viruses

Positive-strand RNA plant viruses that are neither 5′-capped nor 3′-polyadenylated use nontraditional mechanisms to recruit ribosomes to the 5′-end of their viral genomes. One strategy employed by some of these viruses involves a type of RNA element, termed the 3′ cap-independent translation enhancer (3′CITE), located in or near the 3′- untranslated region of viral RNA genomes. 3′CITEs function to mediate efficient translation of 5′-proximally encoded viral proteins and function by recruiting…

Volume 1, Issue 5, 01 November 2011, Pp 373-380
Nicholson, B.L. | White, K.A.

Double-stranded DNA viruses: 20 families and only five different architectural principles for virion assembly

The number of viral particles in the biosphere is enormous. Virus classification helps to comprehend the virosphere and to understand the relationship between different virus groups. However, the evolutionary reach of the currently employed sequence-based approaches in virus taxonomy is rather limited, producing a fragmented view of the virosphere. As a result, viruses are currently classified into 87 different families. However, studies on virion architectures have unexpectedly revealed that…

Volume 1, Issue 2, 01 August 2011, Pp 118-124
Krupovic, M. | Bamford, D.H.

Progress in the development of new therapies for herpesvirus infections

Resurgent interest in antiviral drugs for the treatment of herpesvirus has led to the development of new compounds that are progressing through clinical trials. This is important because there are few therapeutic options for resistant infections and some viruses such as human cytomegalovirus remain underserved. New compounds include conventional DNA polymerase inhibitors such as valomaciclovir and cyclopropavir, as well as CMX001 that has a broad spectrum of antiviral activity that includes all…

Volume 1, Issue 6, 01 December 2011, Pp 548-554
Price, N.B. | Prichard, M.N.

Induction and function of type i and III interferon in response to viral infection

The type I and III interferon (IFN) families consist of cytokines rapidly induced during viral infection that confer antiviral protection on target cells and are critical components of innate immune responses and the transition to effective adaptive immunity. The regulation of their expression involves an intricate and stringently regulated signaling cascade, initiated by recognition most often of viral nucleic acid in cytoplasmic and endosomal compartments and involving a series of protein…

Volume 1, Issue 6, 01 December 2011, Pp 476-486
Levy, D.E. | Marié, I.J. | Durbin, J.E.

Environmental transmission of norovirus gastroenteritis

The advent of molecular techniques and their increasingly widespread use in public health laboratories and research studies has transformed the understanding of the burden of norovirus. Norovirus is the most common cause of community-acquired diarrheal disease across all ages, the most common cause of outbreaks of gastroenteritis, and the most common cause of foodborne disease in the United States. They are a diverse group of single-stranded RNA viruses that are highly infectious and stable in…

Volume 2, Issue 1, 01 February 2012, Pp 96-102
Lopman, B. | Gastañaduy, P. | Park, G.W. | Hall, A.J. | Parashar, U.D. | Vinjé, J.

The genome-linked protein VPg of plant viruses - A protein with many partners

For some plant positive-sense RNA viruses, a protein known as VPg (short for virus protein, genome linked) is covalently linked to the 5′ end of the viral RNA. The VPg is an intrinsically disordered protein, and this property would confer an ability to bind several proteins. Accordingly, the potyvirus VPg interacts with many proteins, notably host factors involved in protein synthesis within viral replication factories or within the nucleus. The number of protein partners, the clustering of the…

Volume 1, Issue 5, 01 November 2011, Pp 347-354
Jiang, J. | Laliberté, J.-F.

Near-atomic resolution cryo-EM for molecular virology

Electron cryo-microscopy (cryo-EM) is a technique in structural biology that is widely used to solve the three-dimensional structures of macromolecular assemblies, close to their biological and solution conditions. Recent improvements in cryo-EM and single-particle reconstruction methodologies have led to the determination of several virus structures at near-atomic resolution (3.3-4.6 Å). These cryo-EM structures not only resolve the Cα backbones and side-chain densities of viral capsid…

Volume 1, Issue 2, 01 August 2011, Pp 110-117
Hryc, C.F. | Chen, D.-H. | Chiu, W.

Late-penetrating viruses

Many enveloped and non-enveloped animal viruses delay the penetration into the cytosol of host cells until they have arrived to endocytic vacuoles deep in the cytoplasm. The late timing is generally determined by a low pH-threshold for the acidactivated penetration process (pH 6.2-4.9), but there can be a combination of other reasons for a delay. Since latepenetrating viruses (L-PVs) must be sorted into the degradative pathway, they are particularly sensitive to perturbations that interfere…

Volume 1, Issue 1, 01 July 2011, Pp 35-43
Lozach, P.-Y. | Huotari, J. | Helenius, A.

Innate immunity modulation in virus entry

Metagenomics and future perspectives in virus discovery

Pathogenesis of respiratory syncytial virus

Rotavirus non-structural proteins: structure and function

Pathogenesis of influenza virus infections: the good, the bad and the ugly

Predicting ‘airborne’ influenza viruses: (trans-) mission impossible?

Interferon-stimulated genes and their antiviral effector functions

Antivirals and resistance: influenza virus

Anti-HCV drugs in the pipeline

Virus entry: old viruses, new receptors