The evolution of viral emergence.
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Adaptation, Physiological↗
Biomedical subjects
Edward C Holmes
Publications and source records attributed to Edward C Holmes.
Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1.
BACKGROUND: Genetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear. RESULTS: We use coalescent methods to quantify the bottleneck in a single case of homosexual transmission and find that over 99% of the env and gag diversity present in the donor is lost. This was consistent with the diversity present at seroconversion in nine other horizontally infected individuals. Furthermore, we estimated viral diversity at birth in 27 infants infected through vertical transmission and found there to be no difference between the two modes of transmission. CONCLUSION: Assuming the bottleneck at transmission is selectively neutral, such a severe reduction in genetic diversity has important implications for adaptation in HIV-1, since beneficial mutations have a reduced chance of transmission.
Bayes Theorem↗
Evolutionary basis of codon usage and nucleotide composition bias in vertebrate DNA viruses.
Understanding the extent and causes of biases in codon usage and nucleotide composition is essential to the study of viral evolution, particularly the interplay between viruses and host cells or immune responses. To understand the common features and differences among viruses we analyzed the genomic characteristics of a representative collection of all sequenced vertebrate-infecting DNA viruses. This revealed that patterns of codon usage bias are strongly correlated with overall genomic GC content, suggesting that genome-wide mutational pressure, rather than natural selection for specific coding triplets, is the main determinant of codon usage. Further, we observed a striking difference in CpG content between DNA viruses with large and small genomes. While the majority of large genome viruses show the expected frequency of CpG, most small genome viruses had CpG contents far below expected values. The exceptions to this generalization, the large gammaherpesviruses and iridoviruses and the small dependoviruses, have sufficiently different life-cycle characteristics that they may help reveal some of the factors shaping the evolution of CpG usage in viruses.
Animals↗
Long-term transmission of defective RNA viruses in humans and Aedes mosquitoes.
In 2001, dengue virus type 1 (DENV-1) populations in humans and mosquitoes from Myanmar acquired a stop-codon mutation in the surface envelope (E) protein gene. Within a year, this stop-codon strain had spread to all individuals sampled. The presence of truncated E protein species within individual viral populations, along with a general relaxation in selective constraint, indicated that the stop-codon strain represents a defective lineage of DENV-1. We propose that such long-term transmission of defective RNA viruses in nature was achieved through complementation by coinfection of host cells with functional viruses.
Aedes↗
Molecular evolution of dengue 2 virus in Puerto Rico: positive selection in the viral envelope accompanies clade reintroduction.
Dengue virus is a circumtropical, mosquito-borne flavivirus that infects 50-100 million people each year and is expanding in both range and prevalence. Of the four co-circulating viral serotypes (DENV-1 to DENV-4) that cause mild to severe febrile disease, DENV-2 has been implicated in the onset of dengue haemorrhagic fever (DHF) in the Americas in the early 1980s. To identify patterns of genetic change since DENV-2's reintroduction into the region, molecular evolution in DENV-2 from Puerto Rico (PR) and surrounding countries was examined over a 20 year period of fluctuating disease incidence. Structural genes (over 20 % of the viral genome), which affect viral packaging, host-cell entry and immune response, were sequenced for 91 DENV-2 isolates derived from both low- and high-prevalence years. Phylogenetic analyses indicated that DENV-2 outbreaks in PR have been caused by viruses assigned to subtype IIIb, originally from Asia. Variation amongst DENV-2 viruses in PR has since largely arisen in situ, except for a lineage-replacement event in 1994 that appears to have non-PR New World origins. Although most structural genes have remained relatively conserved since the 1980s, strong evidence was found for positive selection acting on a number of amino acid sites in the envelope gene, which have also been important in defining phylogenetic structure. Some of these changes are exhibited by the multiple lineages present in 1994, during the largest Puerto Rican outbreak of dengue, suggesting that they may have altered disease dynamics, although their functional significance will require further investigation.
Dengue↗
Isolation of a new strain of the flavivirus cell fusing agent virus in a natural mosquito population from Puerto Rico.
The genus Flavivirus contains approximately 70 single-stranded, positive-sense RNA viruses that are mosquito-borne, tick-borne or have no known vector. Two discoveries support previous suggestions of the existence of a large number of unsampled flaviviruses: (i) a new flavivirus, Kamiti River virus, was recently isolated from Kenyan mosquitoes, and (ii) sequences with high similarity to those of flaviviruses have been found integrated into the genome of Aedes mosquitoes, suggesting a past infection with a virus (or viruses) that has yet to be discovered. These sequences were related most closely to a flavivirus that infects insects alone, cell fusing agent virus (CFAV). CFAV was originally isolated in the laboratory from an Aedes aegypti cell line. To date, this virus had not been found in the wild. In the present study, over 40 isolates of a novel strain of CFAV were discovered from mature mosquitoes sampled from the wild in Puerto Rico. The viral strain was present in a range of mosquito species, including Aedes aegypti, Aedes albopictus and Culex sp., from numerous locations across the island and, importantly, in mosquitoes of both sexes, suggesting vertical transmission. Here, results from viral screening, and cell culture and molecular identification of the infected mosquitoes are presented. Experimental-infection tests were also conducted by using the original CFAV strain and a highly efficient reverse-transcription mechanism has been documented, in which initiation of copying occurs at the 3' terminus of either the genomic RNA or the intermediate of replication, potentially elucidating the mechanism by which flaviviral sequences may have integrated into mosquito genomes.
Aedes↗
Structure and age of genetic diversity of dengue virus type 2 in Thailand.
Dengue virus type 2 (DENV-2) is a common viral infection and an important health concern in South-East Asia. To determine the molecular evolution of DENV-2 in Thailand, 105 isolates of the E (envelope) gene and 10 complete genomes sampled over a 27 year period were sequenced. Phylogenetic analysis of these data revealed that three genotypes of DENV-2 have circulated in Thailand, although, since 1991, only viruses assigned to Asian genotype I have been sampled from the population. A broader analysis of 35 complete genomes of DENV-2 revealed that most amino acids are subject to strong selective constraints, indicative of widespread purifying selection against deleterious mutations. This was further supported by an analysis of genome-wide substitution rates, which indicated that DENV-2 fixes approximately 10 mutations per genome per year, far lower than expected from its mutational dynamics. Finally, estimates of the age of DENV-2 were remarkably consistent among genes, indicating that the current genetic diversity in this virus probably arose within the last 120 years, concordant with the first determination of the aetiology of dengue disease.
Adolescent↗
Comparative analysis reveals no consistent association between the secondary structure of the 3'-untranslated region of dengue viruses and disease syndrome.
A comparative analysis was performed of the 3'-untranslated region (UTR) of Dengue virus (DENV) sampled from Bangkok, Thailand, over a 30 year period and representing all four serotypes. Considerable genetic variation was observed both within and among serotypes. Notably, a full-length version of the critical 3'-long stable hairpin structure was absent from some isolates, suggesting the occurrence of complex structural interactions within the 3'-UTR, including the influence of upstream mutations. The Thai sequences were then combined with 61 globally sampled isolates of DENV taken from patients with either dengue fever or severe dengue disease. No consistent association was found between 3'-UTR secondary structure and the clinical outcome of DENV infection, although some evidence for a trend in this direction was observed in DENV-2. It was concluded that the 3'-UTR is not the sole determinant of DENV virulence in nature, although variation in secondary structure may greatly influence viral fitness.
3' Untranslated Regions↗
Ngoye virus: a novel evolutionary lineage within the genus Flavivirus.
By using degenerate primers deduced from conserved patterns in the flavivirus polymerase gene, a novel RNA virus was discovered in Rhipicephalus ticks sampled from members of the family Bovidae in Senegal. It was named Ngoye virus (NGOV) after the location from which it was isolated. Viral particles could be observed by electron microscopy, but isolation in vertebrate or invertebrate cell lines or by intracerebral infection of newborn mice remained unsuccessful. This is atypical of recognized arboviruses. The characterization of 4176 nt of the non-structural genes revealed that NGOV is a novel flavivirus species. It forms a distinct phylogenetic lineage related distantly to previously identified members of the genus Flavivirus. Analysis of genetic data suggested that the processing of the NGOV polyprotein and the organization of its replication complex are similar to those of flaviviruses. Together with other recent data, these findings suggest that a large number of viruses related distantly to 'classical' arthropod-borne flaviviruses remain to be discovered.
Animals↗
JC virus evolution and its association with human populations.
The ubiquitous human polyomavirus JC (JCV) is a small double-stranded DNA virus that establishes a persistent infection, and it is often transmitted from parents to children. There are at least 14 subtypes of the virus associated with different human populations. Because of its presumed codivergence with humans, JCV has been used as a genetic marker for human evolution and migration. Codivergence has also been used as a basis for estimating the rate of nucleotide substitution in JCV. We tested the hypothesis of host-virus codivergence by (i) performing a reconciliation analysis of phylogenetic trees of human and JCV populations and (ii) providing the first estimate of the evolutionary rate of JCV that is independent from the assumption of codivergence. Strikingly, our comparisons of JCV and human phylogenies provided no evidence for codivergence, suggesting that this virus should not be used as a marker for human population history. Further, while the estimated nucleotide substitution rate of JCV has large confidence intervals due to limited sampling, our analysis suggests that this virus may evolve nearly two orders of magnitude faster than predicted under the codivergence hypothesis.
DNA, Mitochondrial↗
Phylogenetic evidence for the rapid evolution of human B19 erythrovirus.
Human B19 erythrovirus is a ubiquitous viral pathogen, commonly infecting individuals before adulthood. As with all autonomous parvoviruses, its small single-stranded DNA genome is replicated with host cell machinery. While the mechanism of parvovirus genome replication has been studied in detail, the rate at which B19 virus evolves is unknown. By inferring the phylogenetic history and evolutionary dynamics of temporally sampled B19 sequences, we observed a surprisingly high rate of evolutionary change, at approximately 10(-4) nucleotide substitutions per site per year. This rate is more typical of RNA viruses and suggests that high mutation rates are characteristic of the Parvoviridae.
Base Sequence↗
Stochastic processes are key determinants of short-term evolution in influenza a virus.
Understanding the evolutionary dynamics of influenza A virus is central to its surveillance and control. While immune-driven antigenic drift is a key determinant of viral evolution across epidemic seasons, the evolutionary processes shaping influenza virus diversity within seasons are less clear. Here we show with a phylogenetic analysis of 413 complete genomes of human H3N2 influenza A viruses collected between 1997 and 2005 from New York State, United States, that genetic diversity is both abundant and largely generated through the seasonal importation of multiple divergent clades of the same subtype. These clades cocirculated within New York State, allowing frequent reassortment and generating genome-wide diversity. However, relatively low levels of positive selection and genetic diversity were observed at amino acid sites considered important in antigenic drift. These results indicate that adaptive evolution occurs only sporadically in influenza A virus; rather, the stochastic processes of viral migration and clade reassortment play a vital role in shaping short-term evolutionary dynamics. Thus, predicting future patterns of influenza virus evolution for vaccine strain selection is inherently complex and requires intensive surveillance, whole-genome sequencing, and phenotypic analysis.
Antigenic Variation↗
Heading off an influenza pandemic.
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Animals↗
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↗
Lineage extinction and replacement in dengue type 1 virus populations are due to stochastic events rather than to natural selection.
Between 1996 and 1998, two clades (B and C; genotype I) of dengue virus type 1 (DENV-1) appeared in Myanmar (Burma) that were new to that location. Between 1998 and 2000, a third clade (A; genotype III) of DENV-1, which had been circulating at that locality for at least 25 years, became extinct. These changes preceded the largest outbreak of dengue recorded in Myanmar, in 2001, in which more than 95% of viruses recovered from patients were DENV-1, but where the incidence of severe disease was much less than in previous years. Phylogenetic analyses of viral genomes indicated that the two new clades of DENV-1 did not arise from the, now extinct, clade A viruses nor was the extinction of this clade due to differences in the fitness of the viral populations. Since the extinction occurred during an inter-epidemic period, we suggest that it was due to a stochastic event attributable to the low rate of virus transmission in this interval.
Aedes↗
Ancient co-speciation of simian foamy viruses and primates.
Although parasite-host co-speciation is a long-held hypothesis, convincing evidence for long-term co-speciation remains elusive, largely because of small numbers of hosts and parasites studied and uncertainty over rates of evolutionary change. Co-speciation is especially rare in RNA viruses, in which cross-species transfer is the dominant mode of evolution. Simian foamy viruses (SFVs) are ubiquitous, non-pathogenic retroviruses that infect all primates. Here we test the co-speciation hypothesis in SFVs and their primate hosts by comparing the phylogenies of SFV polymerase and mitochondrial cytochrome oxidase subunit II from African and Asian monkeys and apes. The phylogenetic trees were remarkably congruent in both branching order and divergence times, strongly supporting co-speciation. Molecular clock calibrations revealed an extremely low rate of SFV evolution, 1.7 x 10(-8) substitutions per site per year, making it the slowest-evolving RNA virus documented so far. These results indicate that SFVs might have co-speciated with Old World primates for at least 30 million years, making them the oldest known vertebrate RNA viruses.
Animals↗
The hepatitis C virus epidemic among injecting drug users.
Given the economic and health costs of hepatitis C virus (HCV) infection, and the ongoing transmission within the injecting drug user (IDU) population, there is a need for improved understanding of HCV epidemiology within this risk group. We employed a recently developed method based on phylogenetic analysis to infer HCV epidemic history and to provide the first estimates of the rate of spread of subtypes 1a and 3a circulating within injecting drug user populations. The data indicates that HCV subtype 1a entered the IDU population on at least three separate occasions. Both subtypes demonstrate exponential population growth during the 20th century, with a doubling time of 7-8 years. The results provide a baseline for prediction of the future course of the HCV epidemic, and its likely response to transmission control policies.
Disease Outbreaks↗