authoritative, comprehensive and systematic

SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon

Ebolavirus vaccines for humans and apes

How respiratory viruses overcome mucosal defenses and exploit the unique environment of the respiratory tract

Pathogenesis of rhinovirus infection

The interface of animal and human vaccines

The mucosal immune system of the respiratory tract

The role of vaccination in rabies prevention

The pathogenesis of measles

Hendra and Nipah viruses: why are they so deadly?

Crimean–Congo hemorrhagic fever virus: new outbreaks, new discoveries

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.

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.

Emerging zoonotic viruses: New lessons on receptor and entry mechanisms

Viruses enter the host cell by binding cellular receptors that allow appropriate delivery of the viral genome. Although the horizontal propagation of viruses feeds the continuous emergence of novel pathogenic viruses, the genetic variation of cellular receptors can represent a challenging barrier. The SARS coronavirus, henipaviruses and filoviruses are zoonotic RNA viruses that use bats as their reservoir. Their lethality for man has fostered extensive research both on the cellular receptors…

Volume 1, Issue 1, 01 July 2011, Pp 27-34
Gerlier, D.

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.

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.

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.

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.

Viral life cycles captured in three-dimensions with electron microscopy tomography

Viruses hijack host-cell functions and optimize them for viral replication causing a severe threat to human health. However, viruses are also tools to understand cell biology and they may be effective reagents in nanomedicine. Studies from the molecular to cellular levels are aimed at understanding the details of viral life cycles and the underlying virus-host interactions. Recent developments in electron microscopy tomography allow viral and cellular events to be observed in fine structural…

Volume 1, Issue 2, 01 August 2011, Pp 125-133
Fu, C.-Y. | Johnson, J.E.

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.

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.

Viral weapons of membrane destruction: Variable modes of membrane penetration by non-enveloped viruses

Significant progress has recently been obtained in our understanding of cellular entry by nonenveloped viruses (NEVs). A key step in the entry process involves the disruption or remodeling of the limiting cell membrane allowing the virus to gain access to the cellular replication machinery. Biochemical, genetic and structural data from diverse virus groups have shed light on the process ofmembrane penetration thereby revealing both the conservation and divergence of the mechanisms and…

Volume 1, Issue 1, 01 July 2011, Pp 44-49
Moyer, C.L. | Nemerow, G.R.

No acquisition: A new ambition for HIV vaccine development?

Development of a safe and effective prophylactic HIV-1 vaccine presents unique challenges. The pessimism following the failure of two HIV-1 vaccine concepts in clinical trials, HIV-1 gp120 and an adenovirus-based approach to induce only cellular immune responses, has been replaced by cautious optimism engendered by the RV144 trial outcome, the isolation of several new broadly reactive neutralizing monoclonal antibodies, and recent primate model data indicating prevention of viral acquisition by…

Volume 1, Issue 4, 01 October 2011, Pp 246-253
Lakhashe, S.K. | Silvestri, G. | Ruprecht, R.M.

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.

Anti-HCV drugs in the pipeline

Several directly acting and host targeting antivirals that inhibit hepatitis C virus replication have entered clinical trials. Among the most advanced of these are RG7128, an inhibitor of the NS5B polymerase; BMS-790052, an inhibitor of NS5A; and alisporivir, an inhibitor of human cyclophilins. These agents have potent antiviral activity in chronic HCV patients, act additively or synergistically with inhibitors of the HCV NS3/4A protease, and improve the rate of virologic response produced by…

Volume 1, Issue 6, 01 December 2011, Pp 607-616
Yang, P.L. | Gao, M. | Lin, K. | Liu, Q. | Villareal, V.A.

Animal virus schemes for translation dominance

Viruses have adapted a broad range of unique mechanisms to modulate the cellular translational machinery to ensure viral translation at the expense of cellular protein synthesis. Many of these promote virus-specific translation by use of molecular tags on viral mRNA such as internal ribosome entry sites (IRES) and genome-linked viral proteins (VPg) that bind translation machinery components in unusual ways and promote RNA circularization. This review describes recent advances in understanding…

Volume 1, Issue 5, 01 November 2011, Pp 363-372
Reineke, L.C. | Lloyd, R.E.

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.

Natural killer cell responses during viral infections: Flexibility and conditioning of innate immunity by experience

Natural killer (NK) cells mediate innate defense against viral infections, but the mechanisms in place to access their functions as needed during diverse challenges while limiting collateral damage are poorly understood. Recent molecular characterization of effects mediated through infection-induced inhibitory/activating NK receptor-ligand pairs and cytokines are providing new insights into pathways regulating their responses and revealing unexpected consequences for NK cell subset effects,…

Volume 1, Issue 6, 01 December 2011, Pp 497-512
Vidal, S.M. | Khakoo, S.I. | Biron, C.A.

Viral and cellular contributions to herpes simplex virus entry into the cell

Herpes simplex virus (HSV) entry into the cell involves the fusion of the virion envelope with a cellular membrane and delivery of capsid and tegument proteins to the cytoplasm. Our understanding of this phenomenon has greatly increased in recent years. On the virus side, the multipartite nature of the entry-fusion machinery (made of the glycoproteins gD, the heterodimer gH/gL and gB) entails a mechanism of gD activation promoted by the gD encounter with one of its receptor; and cross-talk…

Volume 2, Issue 1, 01 February 2012, Pp 28-36
Campadelli-Fiume, G. | Menotti, L. | Avitabile, E. | Gianni, T.

Herpesvirus microRNAs: Phenotypes and functions

Recently, it has become clear that herpesviruses are unique among pathogenic virus families in that they express multiple virally encoded microRNAs in latently and/or lytically infected cells. The large size and complexity of herpesvirus genomes, combined with the inability of most human herpesviruses to replicate in animals, has until recently limited our ability to examine the contribution of viral microRNAs to herpesvirus replication and pathogenesis in vivo. However, recent data, primarily…

Volume 1, Issue 3, 01 September 2011, Pp 211-215
Cullen, B.R.

Viva la revolución: Rethinking influenza A virus antigenic drift

Rapid antigenic evolution of the influenza A virus hemagglutinin has precluded developing vaccines that provide durable protection. The yearly costs of influenza (circa $10 11 in the USA alone) easily justify investments in better understanding the interaction of influenza with antibodies and other inducible elements of the immune system that potentially limit or circumvent antigenic variation. Here, I summarize exciting new findings that offer the possibility of a quantum improvement in…

Volume 1, Issue 3, 01 September 2011, Pp 177-183
Yewdell, J.W.

Cell entry of enveloped viruses

Infection of cells by enveloped viruses requires merger of the viral envelope membrane with target cell membranes, resulting in the formation of fusion pores through which the viral genome is released. Since lipid membranes do not mix spontaneously, the fusion process is energy-dependent and mediated by viral envelope glycoprotein complexes. On the basis of their structural and mechanistic properties, three distinct classes of viral fusion proteins have been identified to date. Despite their…

Volume 1, Issue 2, 01 August 2011, Pp 92-100
Plemper, R.K.

Lipoprotein component associated with hepatitis C virus is essential for virus infectivity

Many chronic hepatitis patients with hepatitis C virus (HCV) are observed to have a degree of steatosis which is a factor in the progression of liver diseases. Transgenic mice expressing HCV core protein develop liver steatosis before the onset of hepatocellular carcinoma, suggesting active involvement of HCV in the de-regulation of lipid metabolism in host cells. However, the role of lipid metabolism in HCV life cycle has not been fully understood until the establishment of in vitro HCV…

Volume 1, Issue 1, 01 July 2011, Pp 19-26
Shimizu, Y. | Hishiki, T. | Ujino, S. | Sugiyama, K. | Funami, K. | Shimotohno, K.

Evaluating the evidence for virus/host co-evolution

There is currently much debate about the timescales of virus evolution. Some viruses may have co-evolved with human populations for tens of thousands of years, or even with our primate ancestors over many millions of years. However, calibrations of the rate of short-term virus evolution lead to estimates of dates for viral ancestors that are orders of magnitude more recent, and a number of the proposed host-virus co-divergence scenarios have been questioned. Other considerations indicate that…

Volume 1, Issue 5, 01 November 2011, Pp 436-441
Sharp, P.M. | Simmonds, P.

Virus entry: Old viruses, new receptors

The long-sought entry receptors for rubella, sindbis and respiratory syncytial viruses (RV, SV and RSV), together with the missing measles virus (MV) receptor for infection of epithelial cells, were identified in 2011. These have been major developments in the field of virus entry. In addition, 2011 was rich in new information about the interactions of MV, RSV and phleboviruses with DC-SIGN during infection of dendritic cells, a crucial step allowing the virus to breach the epithelial barrier…

Volume 2, Issue 1, 01 February 2012, Pp 4-13
Backovic, M. | Rey, F.A.

Targeted entry of enveloped viruses: measles and herpes simplex virus I

Metagenomics and future perspectives in virus discovery

Resistance to anti-HCV protease inhibitors

Viral and cellular contributions to herpes simplex virus entry into the cell

Poxvirus host cell entry

Is there a future for antiviral fusion inhibitors?

Antivirals and resistance: influenza virus

Anti-HCV drugs in the pipeline

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

Interferon-stimulated genes and their antiviral effector functions