Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “viral evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,711 records · Page 95Linked to original sources
PubMed1997

Gene therapy for lung inflammatory diseases: not so far away?

The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lung diseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for example, overexpressing anti-elastase genes may circumvent elastase mediated lung damage in emphysema. With the development of improved viral and liposome vectors and the evolution of effective adjuvant immunosuppression to obviate host immune responses--for example, using selective cytokines and blockers of T cell surface activation--the potential exists to target therapeutic doses of transgene to deficient or dysregulated cells. Furthermore, increased understanding of tissue-specific promoter regions and of mechanisms controlling regulation of gene expression offer the potential for close control of therapeutic gene expression within the lung. Continuing refinements in these technologies will provide new therapeutic strategies in inflammatory lung disease.

Genetic Therapy↗
PubMed2003

Pancreatic triacylglycerol lipase in a hibernating mammal. I. Novel genomic organization.

Pancreatic triacylglycerol lipase (PTL) is expressed in novel locations during hibernation in the thirteen-lined ground squirrel (Spermophilus tridecemlineatus). PTL cDNAs isolated from two of these locations, heart and white adipose tissue (WAT), contain divergent 5'-untranslated regions (5'-UTRs) suggesting alternative promoter usage or the possibility of multiple PTL genes in the ground squirrel genome. In addition, cDNAs isolated from WAT contain tracts of retroviral sequence in their 5'-UTRs. Our examination of PTL genomic clones isolated from a thirteen-lined ground squirrel genomic DNA library, coupled with genomic Southern blot analysis, enabled us to conclude that PTL mRNAs expressed in heart and WAT are the products of the same single-copy gene. The 5' portion of this gene spans 9.2 kb, is composed of 6 exons, and contains a full-length endogenous retroviral genome with conserved long terminal repeats (LTRs). Alignment of the ground squirrel PTL gene with the mouse, rat, and human PTL genes indicates that this retrovirus inserted into the ground squirrel genome approximately 200 bases upstream of the original PTL transcriptional start site. The insertion is a relatively recent event based on largely intact open-reading frames containing minimal frame-shift and nonsense mutations. The high-percentage identity (99.2%) shared between the 5'- and 3'-LTRs of this endogenous retrovirus suggests that the insertion occurred as recently as 300,000 years ago.

Adipose Tissue↗
PubMed2004

Moderate mutation rate in the SARS coronavirus genome and its implications.

BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 - 2.38 x 10-3 nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 - 3.30 x 10-3 and 1.67 - 4.67 x 10-3 per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.

Coronavirus↗
PubMed2005

Inference of demographic history from genealogical trees using reversible jump Markov chain Monte Carlo.

BACKGROUND: Coalescent theory is a general framework to model genetic variation in a population. Specifically, it allows inference about population parameters from sampled DNA sequences. However, most currently employed variants of coalescent theory only consider very simple demographic scenarios of population size changes, such as exponential growth. RESULTS: Here we develop a coalescent approach that allows Bayesian non-parametric estimation of the demographic history using genealogies reconstructed from sampled DNA sequences. In this framework inference and model selection is done using reversible jump Markov chain Monte Carlo (MCMC). This method is computationally efficient and overcomes the limitations of related non-parametric approaches such as the skyline plot. We validate the approach using simulated data. Subsequently, we reanalyze HIV-1 sequence data from Central Africa and Hepatitis C virus (HCV) data from Egypt. CONCLUSIONS: The new method provides a Bayesian procedure for non-parametric estimation of the demographic history. By construction it additionally provides confidence limits and may be used jointly with other MCMC-based coalescent approaches.

Algorithms↗
PubMed2005

Whole-genome analysis of human influenza A virus reveals multiple persistent lineages and reassortment among recent H3N2 viruses.

Understanding the evolution of influenza A viruses in humans is important for surveillance and vaccine strain selection. We performed a phylogenetic analysis of 156 complete genomes of human H3N2 influenza A viruses collected between 1999 and 2004 from New York State, United States, and observed multiple co-circulating clades with different population frequencies. Strikingly, phylogenies inferred for individual gene segments revealed that multiple reassortment events had occurred among these clades, such that one clade of H3N2 viruses present at least since 2000 had provided the hemagglutinin gene for all those H3N2 viruses sampled after the 2002-2003 influenza season. This reassortment event was the likely progenitor of the antigenically variant influenza strains that caused the A/Fujian/411/2002-like epidemic of the 2003-2004 influenza season. However, despite sharing the same hemagglutinin, these phylogenetically distinct lineages of viruses continue to co-circulate in the same population. These data, derived from the first large-scale analysis of H3N2 viruses, convincingly demonstrate that multiple lineages can co-circulate, persist, and reassort in epidemiologically significant ways, and underscore the importance of genomic analyses for future influenza surveillance.

Evolution, Molecular↗
PubMed2006

The fittest versus the flattest: experimental confirmation of the quasispecies effect with subviral pathogens.

The "survival of the fittest" is the paradigm of Darwinian evolution in which the best-adapted replicators are favored by natural selection. However, at high mutation rates, the fittest organisms are not necessarily the fastest replicators but rather are those that show the greatest robustness against deleterious mutational effects, even at the cost of a low replication rate. This scenario, dubbed the "survival of the flattest", has so far only been shown to operate in digital organisms. We show that "survival of the flattest" can also occur in biological entities by analyzing the outcome of competition between two viroid species coinfecting the same plant. Under optimal growth conditions, a viroid species characterized by fast population growth and genetic homogeneity outcompeted a viroid species with slow population growth and a high degree of variation. In contrast, the slow-growth species was able to outcompete the fast species when the mutation rate was increased. These experimental results were supported by an in silico model of competing viroid quasispecies.

Chrysanthemum↗
PubMed2026

Novel insights into tomato leaf curl New Delhi virus introduction and evolution in Southeastern France using an advanced long-read sequencing workflow.

The Mediterranean population of tomato leaf curl New Delhi virus (ToLCNDV-ES) is characterized by a high genetic uniformity, distinguishing it from its Asian counterparts. ToLCNDV-ES is thought to have a monophyletic origin, likely resulting from a single recombination event, prior to its spread throughout the Mediterranean region. Following its first detection in southeastern France in 2020, ToLCNDV-ES re-emerged in France in 2022. Our analysis based on advanced long-read sequencing, circular DNA profiling, and phylogeny indicates both local persistence of French ToLCNDV-ES and multiple independent introduction events. Signatures of positive selection were identified in French ToLCNDV-ES populations, whereas no clear evidence of recombination was found. Bayesian time-structured phylogenetic analyses suggest that introductions in France occurred between 2018 and 2021 from the major ToLCNDV-ES clade, while several Italian ToLCNDV-ES isolates diverged prior to the virus introduction in the Mediterranean basin. Overall, this study demonstrates the value of an optimized long-read sequencing approach for resolving circular DNA virus diversity, and sheds light on the complex evolutionary history of ToLCNDV-ES in the Mediterranean Basin, particularly in southeastern France.

France↗
PubMed1996

A novel endogenous mouse mammary tumor virus locus in Asian wild mice and its evolutionary divergency.

The divergency of endogenous mouse mammary tumor virus (MMTV) in European mouse strains indicates acquisition of exogenous MMTV into their genomes during evolution. In the present study, we selected two strains of Asian wild mice, Cas-Hmi (Mus musculus castaneus) and Sub-Kjr (M. m. subspecies) to investigate a possible divergency of endogenous MMTVs among Asian mouse strains. Southern blot analysis and polymerase chain reaction (PCR) demonstrated that Cas-Hmi and Sub-Kjr have the full structure of integrated endogenous MMTVs, suggesting that these mice were diverged during evolution after MMTV endemics.

Animals↗
PubMed2006

Bioinformatics research on the SARS coronavirus (SARS_CoV) in China.

Severe acute respiratory syndrome (SARS) first appeared in 2002 in China, which fastly affected about 8000 patients over 29 countries and caused 774 fatalities. As its pathogen was identified as a new kind of coronavirus (SARS_CoV), its genome was quickly sequenced on several isolates. Studies on its functional genomics were performed by combinatorial application of all the available bioinformatics tools and the development of new programs. In this way, it was found that the four proteins were absolutely responsible for nosogenesis of SARS, i.e. spike (S) protein; small envelop (E) protein; membrane (M) protein; and nucleocaspid (N) protein. Molecular evolution studies have revealed that SARS must be originated from wild animals, and it was demonstrated that the major genetic variations in some critical genes, particularly the Spike gene, was essential for the transition from animal-to-human transmission to human-to-human transmission. Theoretical models, either Logistic model or SIR model, were developed to describe the transmission of SARS. The recorded difference of SARS spreading in Beijing and Hong Kong was also reasonably analyzed according to these models. The whole process of fruitful bioinformatics studies, along with other related scientific investigations have set up an unprecedented paradigm for human of how to battle against sudden-breaking and catastrophic epidemics.

China↗
PubMed2006

RNA as a target for host defense and anti-HIV drugs.

Viruses have many strategies for negotiating entry into cells and harnessing the cellular machinery for their propagation. The diversity of strategies is however bound by the central process of translating protein from RNA. The co-evolution of cellular responses to signature viral RNA intermediates and the counter measures employed by viruses, highlight the vulnerability of this aspect of viral replication and the potential of viral RNA as a drug target. In this review we will discuss novel efforts to target the RNA intermediates of the HIV life cycle.

Anti-HIV Agents↗
PubMed2005

Hantaviruses: molecular biology, evolution and pathogenesis.

Hantaviruses are tri-segmented negative sense single stranded RNA viruses that belong to the family Bunyaviridae. In nature, hantaviruses are exclusively maintained in the populations of their specific rodent hosts. In their natural host species, hantaviruses usually develop a persistent infection with prolonged virus shedding in excreta. Humans become infected by inhaling virus contaminated aerosol. Unlike asymptomatic infection in rodents, hantaviruses cause two acute febrile diseases in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The mortality rate varies from 0.1% to 40% depending on the virus involved. Hantaviruses are distributed world wide, with over 150,000 HFRS and HPS cases being registered annually. In this review we summarize current knowledge on hantavirus molecular biology, epidemiology, genetic diversity and co-evolution with rodent hosts. In addition, special attention was given in this review to describing clinical manifestation of HFRS and HPS, and advances in our current understanding of the host immune response, treatment, and prevention.

Animals↗
PubMed1993

Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences.

Despite the rapid mutational change that is typical of positive-strand RNA viruses, enzymes mediating the replication and expression of virus genomes contain arrays of conserved sequence motifs. Proteins with such motifs include RNA-dependent RNA polymerase, putative RNA helicase, chymotrypsin-like and papain-like proteases, and methyltransferases. The genes for these proteins form partially conserved modules in large subsets of viruses. A concept of the virus genome as a relatively evolutionarily stable "core" of housekeeping genes accompanied by a much more flexible "shell" consisting mostly of genes coding for virion components and various accessory proteins is discussed. Shuffling of the "shell" genes including genome reorganization and recombination between remote groups of viruses is considered to be one of the major factors of virus evolution. Multiple alignments for the conserved viral proteins were constructed and used to generate the respective phylogenetic trees. Based primarily on the tentative phylogeny for the RNA-dependent RNA polymerase, which is the only universally conserved protein of positive-strand RNA viruses, three large classes of viruses, each consisting of distinct smaller divisions, were delineated. A strong correlation was observed between this grouping and the tentative phylogenies for the other conserved proteins as well as the arrangement of genes encoding these proteins in the virus genome. A comparable correlation with the polymerase phylogeny was not found for genes encoding virion components or for genome expression strategies. It is surmised that several types of arrangement of the "shell" genes as well as basic mechanisms of expression could have evolved independently in different evolutionary lineages. The grouping revealed by phylogenetic analysis may provide the basis for revision of virus classification, and phylogenetic taxonomy of positive-strand RNA viruses is outlined. Some of the phylogenetically derived divisions of positive-strand RNA viruses also include double-stranded RNA viruses, indicating that in certain cases the type of genome nucleic acid may not be a reliable taxonomic criterion for viruses. Hypothetical evolutionary scenarios for positive-strand RNA viruses are proposed. It is hypothesized that all positive-strand RNA viruses and some related double-stranded RNA viruses could have evolved from a common ancestor virus that contained genes for RNA-dependent RNA polymerase, a chymotrypsin-related protease that also functioned as the capsid protein, and possibly an RNA helicase.

Amino Acid Sequence↗