http://www.mdpi.com/journal/viruses/special_issues/virus-dynamics/ Dear Colleagues, In this special edition of “Viruses” on Virus Dynamics and Evolution, we focus on new approaches and systems that enhance our knowledge of how viruses adapt and persist within hosts and within populations. There are now unprecedented opportunities to study the interaction of virus and host at these multiple scales due in part to major advances in sequencing and single cell or molecule imaging. Changes in empirical methods are accompanied by substantial progress in computational algorithms and mathematical modeling, which are needed to effectively synthesize these high dimensional and complex data. Indeed, the field of virus dynamics and evolution is exemplary for integrating theory and data to achieve a more complete understanding of virus-host interactions. This compilation of papers exemplifies recent advances in this exciting field. Prof. Dr. Mary Poss Guest Editor{snippet name="submission_info"} http://www.mdpi.com/1999-4915/3/8/1432/ Viruses have attracted the interest of researchers from multiple disciplines and have nucleated many productive and innovative collaborations. In part, this is because viruses so intimately associate with their hosts that decoupling host and virus biology is difficult, and virus-host interactions occur at multiple scales, from within cells to populations, each of which is intrinsically complex. As a consequence, ecologists, population biologists, evolutionary biologists, and researchers from quantitative fields, including mathematics, statistics, physics and computer science, make significant contributions to the field of virology. Our understanding of virus dynamics and evolution has substantially benefited from these multidisciplinary efforts. It is now common to see advanced phylogenetic reconstruction methods used to determine the origins of emergent viruses, to estimate the effect of natural selection on virus populations, and to assess virus population dynamics. Mathematical and statistical models that elucidate complex virus and host interactions in time and space at the molecular and population level are appearing more regularly in virology and biomedical journals. Massive quantities of data now available due to technological innovation in imaging, increased disease surveillance efforts, and novel approaches to determine social contact structure are changing approaches to study the dynamics and evolution of viral infections in heterogeneous environments. The next decade presents exciting new opportunities and challenges for the expanding field of researchers investigating dynamics of viral infections that will lead to innovation and new insight on virus interactions in both individual hosts and in populations. The compilation of articles in this Special Issue on “Virus Dynamics and Evolution” is comprised of reviews and primary research, summarized below, that provide new perspectives on virus interactions with host organisms through the integration of empirical and computational analyses of virus at molecular, cellular, and population levels. http://www.mdpi.com/1999-4915/3/8/1432/ Tue, 16 Aug 2011 00:00:00 CEST Viruses 2011-08-16 3 8 Editorial 1432 1438 1999-4915 Virus Dynamics and Evolution: Bridging Scales and Disciplines 2011-08-16 doi: 10.3390/v3081432 Mary Poss http://www.mdpi.com/1999-4915/3/6/659/ Networks are often used to model the contact processes that allow pathogens to spread between hosts but it remains unclear which models best describe these networks. One question is whether clustering in networks, roughly defined as the propensity for triangles to form, affects the dynamics of disease spread. We perform a simulation study to see if there is a signal in epidemic transmission trees of clustering. We simulate susceptible-exposed-infectious-removed (SEIR) epidemics (with no re-infection) over networks with fixed degree sequences but different levels of clustering and compare trees from networks with the same degree sequence and different clustering levels. We find that the variation of such trees simulated on networks with different levels of clustering is barely greater than those simulated on networks with the same level of clustering, suggesting that clustering can not be detected in transmission data when re-infection does not occur. http://www.mdpi.com/1999-4915/3/6/659/ Fri, 03 Jun 2011 00:00:00 CEST Viruses 2011-06-03 3 6 Article 659 676 1999-4915 Is Network Clustering Detectable in Transmission Trees? 2011-06-03 doi: 10.3390/v3060659 David Welch http://www.mdpi.com/1999-4915/3/4/379/ The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues. http://www.mdpi.com/1999-4915/3/4/379/ Fri, 15 Apr 2011 00:00:00 CEST Viruses 2011-04-15 3 4 Review 379 397 1999-4915 An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses 2011-04-15 doi: 10.3390/v3040379 Kurt J. Vandegrift Nina Wale Jonathan H. Epstein http://www.mdpi.com/1999-4915/3/2/83/ Hepatitis B virus (HBV) genomes are small, semi-double-stranded DNA circular genomes that contain alternating overlapping reading frames and replicate through an RNA intermediary phase. This complex biology has presented a challenge to estimating an evolutionary rate for HBV, leading to difficulties resolving the evolutionary and epidemiological history of the virus. Here, we re-examine rates of HBV evolution using a novel data set of 112 within-host, transmission history (pedigree) and among-host genomes isolated over 20 years from the indigenous peoples of the South Pacific, combined with 313 previously published HBV genomes. We employ Bayesian phylogenetic approaches to examine several potential causes and consequences of evolutionary rate variation in HBV. Our results reveal rate variation both between genotypes and across the genome, as well as strikingly slower rates when genomes are sampled in the Hepatitis B e antigen positive state, compared to the e antigen negative state. This Hepatitis B e antigen rate variation was found to be largely attributable to changes during the course of infection in the preCore and Core genes and their regulatory elements. http://www.mdpi.com/1999-4915/3/2/83/ Tue, 25 Jan 2011 00:00:00 CET Viruses 2011-01-25 3 2 Article 83 101 1999-4915 Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation 2011-01-25 doi: 10.3390/v3020083 Abby Harrison Philippe Lemey Matthew Hurles Chris Moyes Susanne Horn Jan Pryor Joji Malani Mathias Supuri Andrew Masta Burentau Teriboriki Tebuka Toatu David Penny Andrew Rambaut Beth Shapiro http://www.mdpi.com/1999-4915/3/1/12/ Although generally regarded as pathogens, viruses can also be mutualists. A number of examples of extreme mutualism (i.e., symbiogenesis) have been well studied. Other examples of mutualism are less common, but this is likely because viruses have rarely been thought of as having any beneficial effects on their hosts. The effect of mutualism on the population dynamics of viruses is a topic that has not been addressed experimentally. However, the potential for understanding mutualism and how a virus might become a mutualist may be elucidated by understanding these dynamics. http://www.mdpi.com/1999-4915/3/1/12/ Mon, 17 Jan 2011 00:00:00 CET Viruses 2011-01-17 3 1 Commentary 12 19 1999-4915 Changes in Population Dynamics in Mutualistic versus Pathogenic Viruses 2011-01-17 doi: 10.3390/v3010012 Marilyn J. Roossinck http://www.mdpi.com/1999-4915/3/1/1/ The ability of lentiviruses to continually evolve and escape immune control is the central impediment in developing an effective vaccine for HIV-1 and other lentiviruses. Equine infectious anemia virus (EIAV) is considered a useful model for immune control of lentivirus infection. Virus-specific cytotoxic T lymphocytes (CTL) and broadly neutralizing antibody effectively control EIAV replication during inapparent stages of disease, but after years of low-level replication, the virus is still able to produce evasion genotypes that lead to late re-emergence of disease. There is a high rate of genetic variation in the EIAV surface envelope glycoprotein (SU) and in the region of the transmembrane protein (TM) overlapped by the major exon of Rev. This review examines genetic and phenotypic variation in Rev during EIAV disease and a possible role for Rev in immune evasion and virus persistence. http://www.mdpi.com/1999-4915/3/1/1/ Tue, 11 Jan 2011 00:00:00 CET Viruses 2011-01-11 3 1 Review 1 11 1999-4915 Rev Variation during Persistent Lentivirus Infection 2011-01-11 doi: 10.3390/v3010001 Susan Carpenter Wei-Chen Chen Karin S. Dorman http://www.mdpi.com/1999-4915/2/12/2782/ The cell response to virus infection and virus perturbation of that response is dynamic and is reflected by changes in cell susceptibility to infection. In this study, we evaluated the response of human epithelial cells to sequential infections with human respiratory syncytial virus strains A2 and B to determine if a primary infection with one strain will impact the ability of cells to be infected with the second as a function of virus strain and time elapsed between the two exposures. Infected cells were visualized with fluorescent markers, and location of all cells in the tissue culture well were identified using imaging software. We employed tools from spatial statistics to investigate the likelihood of a cell being infected given its proximity to a cell infected with either the homologous or heterologous virus. We used point processes, K-functions, and simulation procedures designed to account for specific features of our data when assessing spatial associations. Our results suggest that intrinsic cell properties increase susceptibility of cells to infection, more so for RSV-B than for RSV-A. Further, we provide evidence that the primary infection can decrease susceptibility of cells to the heterologous challenge virus but only at the 16 h time point evaluated in this study. Our research effort highlights the merits of integrating empirical and statistical approaches to gain greater insight on in vitro dynamics of virus-host interactions. http://www.mdpi.com/1999-4915/2/12/2782/ Wed, 22 Dec 2010 00:00:00 CET Viruses 2010-12-22 2 12 Article 2782 2802 1999-4915 Exploratory Spatial Analysis of in vitro Respiratory Syncytial Virus Co-infections 2010-12-22 doi: 10.3390/v2122782 Ivan Simeonov Xiaoyan Gong Oekyung Kim Mary Poss Francesca Chiaromonte John Fricks http://www.mdpi.com/1999-4915/2/12/2663/ CD4 decline is a hallmark of disease onset in individuals infected with Feline Immunodeficiency Virus (FIV) or Human Immunodeficiency Virus type 1 (HIV-1). Cats that are infected with a poorly replicating, apathogenic FIV (PLV) prior to exposure to a virulent FIV strain (FIVC) maintain CD4 numbers by mechanisms that are not correlated with a measurable adaptive immune response or reduction in circulating viral load. We employed population genetic approaches based on the 3' portion of the viral genome to estimate the population structure of FIVC from single and dual infected cats. In dual infected cats, FIVC effective population size was decreased during the initial viral expansion phase, and after three weeks of infection, the population declined sharply. The FIVC population recovered to pre-bottleneck levels approximately seven weeks post-FIVC infection. However, the population emerging from the bottleneck in dual infected cats was distinct based on estimates of temporal population structure and substitution profiles. The transition to transversion rate ratio (k) increased from early to late phases in dual infected cats due primarily to a decrease in transversions whereas in single infected cats, k declined over time. Although one clone with extensive G to A substitutions, indicative of host cytidine deaminase editing, was recovered from a dual infected cat during the bottleneck, the post bottleneck population had an overall reduction in G to A substitutions. These data are consistent with a model of PLV-induced host restriction, putatively involving host DNA editing, that alters the dynamics of FIVC throughout the course of infection leading to disease attenuation. http://www.mdpi.com/1999-4915/2/12/2663/ Fri, 10 Dec 2010 00:00:00 CET Viruses 2010-12-10 2 12 Article 2663 2680 1999-4915 Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection 2010-12-10 doi: 10.3390/v2122663 Abinash Padhi Howard Ross Julie Terwee Sue VandeWoude Mary Poss http://www.mdpi.com/1999-4915/2/12/2594/ Arthropod-borne viruses (arboviruses) are maintained in nature by cycling between vertebrate hosts and haematophagous invertebrate vectors. These viruses are responsible for causing a significant public health burden throughout the world, with over 100 species having the capacity to cause human disease. Arbovirus outbreaks in previously naïve environments demonstrate the potential of these pathogens for expansion and emergence, possibly exacerbated more recently by changing climates. These recent outbreaks, together with the continued devastation caused by endemic viruses, such as Dengue virus which persists in many areas, demonstrate the need to better understand the selective pressures that shape arbovirus evolution. Specifically, a comprehensive understanding of host-virus interactions and how they shape both host-specific and virus‑specific evolutionary pressures is needed to fully evaluate the factors that govern the potential for host shifts and geographic expansions. One approach to advance our understanding of the factors influencing arbovirus evolution in nature is the use of experimental studies in the laboratory. Here, we review the contributions that laboratory passage and experimental infection studies have made to the field of arbovirus adaptation and evolution, and how these studies contribute to the overall field of arbovirus evolution. In particular, this review focuses on the areas of evolutionary constraints and mutant swarm dynamics; how experimental results compare to theoretical predictions; the importance of arbovirus ecology in shaping viral swarms; and how current knowledge should guide future questions relevant to understanding arbovirus evolution. http://www.mdpi.com/1999-4915/2/12/2594/ Thu, 02 Dec 2010 00:00:00 CET Viruses 2010-12-02 2 12 Review 2594 2617 1999-4915 Insights into Arbovirus Evolution and Adaptation from Experimental Studies 2010-12-02 doi: 10.3390/v2122594 Alexander T. Ciota Laura D. Kramer