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At least 829 records · Page 46Linked to original sources
PubMed1982

Evolution of influenza A and B viruses: conservation of structural features in the hemagglutinin genes.

The complete nucleotide sequence of the hemagglutinin (HA) gene of a type B influenza virus (B/Lee/40) was obtained by using cloned cDNA derived from the RNA segment. The gene is 1,882 nucleotides long and can code for a protein precursor of 584 amino acids. Structural features common to type A virus HAs are also conserved in the B virus HA. These include a hydrophobic signal peptide, hydrophobic NH2 and COOH termini of the HA2 subunit, and a HA1/HA2 cleavage site involving an arginine residue. The sequence of the B HA gene and its deduced amino acid sequence were compared to those of a type A influenza virus (A/PR/8/34). When these two genes were aligned, it was found that 24% of the amino acids in the HA1 subunits and 39% of the amino acids in the HA2 subunits are conserved. This degree of relatedness between type B virus and type A virus HAs (intertypic comparison) is similar to the homologies observed among certain type A virus HAs (intratypic comparison). A close evolutionary relationship is therefore suggested between the HAs of type A and type B influenza viruses.

Amino Acid Sequence↗
PubMed2004

Viral evolution and the emergence of SARS coronavirus.

The recent appearance of severe acute respiratory syndrome coronavirus (SARS-CoV) highlights the continual threat to human health posed by emerging viruses. However, the central processes in the evolution of emerging viruses are unclear, particularly the selection pressures faced by viruses in new host species. We outline some of the key evolutionary genetic aspects of viral emergence. We emphasize that, although the high mutation rates of RNA viruses provide them with great adaptability and explain why they are the main cause of emerging diseases, their limited genome size means that they are also subject to major evolutionary constraints. Understanding the mechanistic basis of these constraints, particularly the roles played by epistasis and pleiotropy, is likely to be central in explaining why some RNA viruses are more able than others to cross species boundaries. Viral genetic factors have also been implicated in the emergence of SARS-CoV, with the suggestion that this virus is a recombinant between mammalian and avian coronaviruses. We show, however, that the phylogenetic patterns cited as evidence for recombination are more probably caused by a variation in substitution rate among lineages and that recombination is unlikely to explain the appearance of SARS in humans.

Databases, Nucleic Acid↗
PubMed2001

Emergence of a distinct pattern of viral mutations in chimpanzees infected with a homogeneous inoculum of hepatitis C virus.

BACKGROUND & AIMS: Prospective, long-term study of viral evolution and immunologic responses in chimpanzees infected with a homogeneous hepatitis C virus (HCV) population is crucial in understanding the pathogenesis of HCV-host interactions. METHODS: A molecular clone was constructed of HCV genotype 1b and RNA transcribed from this clone inoculated intrahepatically into chimpanzee X0142. Serum was taken from X0142 at week 2 and inoculated intravenously into a second chimpanzee (X0234). Detailed virologic, serologic, and immunologic analyses of these 2 chimpanzees were performed. RESULTS: Both chimpanzees developed persistent viremia, with titers of 10(3) to 10(5) genomes/mL, for 80 weeks (X0142) and 55 weeks (X0234) of follow-up. A late antibody response against the nonstructural proteins and a weak, transient T-helper proliferative response were detected in both animals. In X0142, 25 mutations emerged in the virus population by week 78 and 15 in X0234 by week 35. A relatively large proportion of mutations affecting protein sequences appeared in the NS5A gene (33% in X0142 and X0234 combined), and 5 mutations were common to both chimpanzees. CONCLUSIONS: In this long-term study of the molecular evolution of HCV genotype 1b from a cloned source, the appearance of a distinct pattern of mutations is suggestive of an adaptive response of HCV in vivo. In addition, a limited virus-specific immunity may contribute to HCV persistence.

Alanine Transaminase↗
PubMed1991

Subviral pathogens of plants: viroids and viroidlike satellite RNAs.

Contrary to earlier beliefs, viruses are not the smallest causative agents of infectious diseases. Single-stranded RNAs as small as 246 nucleotides exist in certain higher plants and cause more than a dozen crop diseases. These RNAs have been termed viroids. Despite their extremely limited information content, viroids replicate autonomously in susceptible cells--that is, they do not require helper functions from simultaneously replicating conventional viruses. Viroids are covalently closed circular molecules with a characteristic rodlike secondary structure in which short helical regions are interrupted by internal and bulge loops. Viroids are not translated; they are replicated by a host enzyme (or enzymes) (probably RNA polymerase II) via oligomeric RNA intermediates by a rolling circle mechanism. Viroidlike satellite RNAs resemble viroids in size and molecular structure, but are found within the capsids of specific helper viruses on which they depend for their own replication. These RNAs are of great interest to molecular biology for at least two reasons: 1) they are the smallest and simplest replicating molecules known, and 2) they may represent living fossils of precellular evolution in a hypothetical RNA world.

Base Sequence↗
PubMed2005

Identification and visualization of the dimerization initiation site of the prototype lentivirus, maedi visna virus: a potential GACG tetraloop displays structural homology with the alpha- and gamma-retroviruses.

Dimerization of retroviral genomic RNA is essential for efficient viral replication and is mediated by structural interactions between identical RNA motifs in the viral leader region. We have visualized, by electron microscopy, RNA dimers formed from the leader region of the prototype lentivirus, maedi visna virus. Characterization by in vitro assays of the domains responsible for this interaction has identified a 20 nucleotide sequence that functions as the core dimerization initiation site. This region is predicted to form a GACG tetraloop and therefore differs significantly from the kissing loop palindromes utilized to initiate dimerization in primate lentiviruses. The motif is strongly conserved across the ovine and caprine lentiviruses, implying a critical functional role. Furthermore, the proposed GACG tetraloop exhibits marked structural homology with similar structural motifs present in the leader regions of the alpha- and gamma-retroviruses, and the maedi visna virus dimer linkage region is capable of forming heterodimeric species with the Moloney murine leukemia virus Psi domain. This may be indicative of commonality of origin of the two viruses or convergent evolution.

Animals↗
PubMed1987

Molecular epizootiology and evolution of vesicular stomatitis virus New Jersey.

Vesicular stomatitis virus (VSV) has been shown previously to be capable of undergoing rapid mutational change during sequential experimental infections in various tissue culture cell systems (J. Holland, K. Spindler, F. Horodyski, E. Grabau, S. Nichol, and S. Vandepol, Science 215:1577-1585, 1982). The present study was undertaken to determine the degree of genetic diversity and evolution of the virus under natural infection conditions and to gain insight into the epizootiology of the disease. Between 1982 and 1985, numerous outbreaks of VSV of the New Jersey serotype were reported throughout regions of the United States and Mexico. A T1 RNase fingerprint analysis was performed on the RNA genomes of 43 virus isolates from areas of epizootic and enzootic virus activity. This indicates that virus populations were genetically relatively homogeneous within successive U.S. virus epizootics. The data included virus isolates from different epizootic stages, geographical locations, host animals, and host lesion sites. In contrast, only distant genome RNA T1 fingerprint similarities were observed among viruses of the different U.S. epizootics. However, Mexican viruses isolated before or concurrent with U.S. epizootics had very similar RNA genome fingerprints, suggesting that Mexico may have been the possible origin of virus initiating recent U.S. VSV New Jersey outbreaks. Comparison of T1 fingerprints of viruses with enzootic disease areas revealed a greater extent of virus genetic diversity in these areas relative to that observed in epizootic areas. The evolutionary significance of these findings and their relationship to experimental data on VSV evolution are discussed.

Animals↗
PubMed2005

Co-evolutionary patterns of variation in small and large RNA segments of Crimean-Congo hemorrhagic fever virus.

The genus Nairovirus of the family Bunyaviridae includes the Crimean-Congo haemorrhagic fever (CCHF) species group. The species is predominated by the hazard-group 4 pathogens, from which the name and majority of strain entries are derived. Additionally, the species embraces hazard-group 2 viruses that are classified as members by antigenic cross-reactivity. CCHF viruses have a tripartite RNA genome consisting of large (L), medium (M) and small (S) segments. Here, the sequence characterization of previously undescribed L and S segments from novel strains originating in the Middle East and Africa is reported. Further scrutiny of this data with phylogenetic tools, in the context of other publicly available sequence information, reveals analogous grouping patterns between the L and S segments. These groups correlate with the geographical distribution of strain isolation and indicate that the L and S segments of CCHF viruses have evolved together.

Africa↗
PubMed1995

Response of foot-and-mouth disease virus C3 Resende to immunological pressure exerted in vitro by antiviral polyclonal sera.

The foot-and-mouth disease virus (FMDV) shows a remarkable antigenic variability. Like other RNA viruses, FMDV has a high mutation rate and it has been proposed that selection exerted by antibodies of the host could play a major role in its evolution. In this work, antiserum-resistant variants of FMDV (Nr variants) were selected upon 25 serial passages of a cloned C3 Resende strain on secondary monolayers of fetal bovine kidney (FBK-2) cells in the presence of subneutralizing levels of antiviral polyclonal sera (APS). After serial passage under immune selective pressure, the five Nr variant populations selected from five independent serial passages--their controls remaining unmodified--acquired the following characteristics: (i) increased resistance to neutralization by APS; (ii) five different antigenic specificities detected by enzyme-linked and neutralization assays using monoclonal antibodies; (iii) the same modification (residue 146, S to L) at the major antigenic site of VP1 (G-H loop, the 135-160 region); and (iv) specific changes for each Nr population outside the major antigenic site of VP1 at residues 46, 48 and 49 of the 40-60 region of VP1 (B-C loop). These results extend our previous work on selection of Nr variants using polyclonal sera, and add new information with regard to antigenic variation, mainly concerning the involvement of the 40-60 region of VP1 in the process of immune selection.

Amino Acid Sequence↗
PubMed1999

Spontaneous mutation rate of measles virus: direct estimation based on mutations conferring monoclonal antibody resistance.

High mutation rates typical of RNA viruses often generate a unique viral population structure consisting of a large number of genetic microvariants. In the case of viral pathogens, this can result in rapid evolution of antiviral resistance or vaccine-escape mutants. We determined a direct estimate of the mutation rate of measles virus, the next likely target for global elimination following poliovirus. In a laboratory tissue culture system, we used the fluctuation test method of estimating mutation rate, which involves screening a large number of independent populations initiated by a small number of viruses each for the presence or absence of a particular single point mutation. The mutation we focused on, which can be screened for phenotypically, confers resistance to a monoclonal antibody (MAb 80-III-B2). The entire H gene of a subset of mutants was sequenced to verify that the resistance phenotype was associated with single point mutations. The epitope conferring MAb resistance was further characterized by Western blot analysis. Based on this approach, measles virus was estimated to have a mutation rate of 9 x 10(-5) per base per replication and a genomic mutation rate of 1.43 per replication. The mutation rates we estimated for measles virus are comparable to recent in vitro estimates for both poliovirus and vesicular stomatitis virus. In the field, however, measles virus shows marked genetic stability. We briefly discuss the evolutionary implications of these results.

Animals↗
PubMed1988

Completion of the rabies virus genome sequence determination: highly conserved domains among the L (polymerase) proteins of unsegmented negative-strand RNA viruses.

We have now completed the rabies genome structure by the cloning and the sequencing of the entire L gene and the 5' untranscribed region. The L gene encodes a single open reading frame 2142 amino acids in length (244,206 Da) that corresponds to the viral RNA-dependent RNA polymerase. In contrast with other isofunctional proteins, the rabies polymerase exhibits a high degree of homology with the vesicular stomatitis virus polymerase, and a lesser degree, although significant, with those of Sendai virus and Newcastle disease virus, which suggests a differential evolution of the different cistrons. We have observed several strongly conserved stretches which may designate the independent functional domains of this multifunctional protein. In addition to the conservation of related transcription signals (N. Tordo et al. (1986) Proc. Natl. Acad. Sci. USA 83, 3914-3918.), this highlights the striking selective pressure on elements involved in transcription and replication mechanisms, and provides further evidence for a common ancestry of Rhabdoviridae and Paramyxoviridae families. The terminal complementarity observed in the rabies genome suggests the conservation of important genomic signals.

Amino Acid Sequence↗
PubMed2027

Nanopore Sequencing for Chikungunya Virus: Principles and Application.

Nanopore sequencing is transforming viral genomics through real-time, portable, long-read analysis of RNA and DNA. Unlike traditional short-read platforms, it detects nucleotide sequences by measuring ionic current changes as nucleic acids pass through nanoscale pores, enabling direct single-molecule sequencing and base modification detection. Its simplicity, flexibility, and capacity for ultra-long reads make it ideal for resolving complex genomic regions, structural variants, and full viral genomes. These advantages have accelerated its use in pathogen surveillance and outbreak response, especially in resource-limited settings. For chikungunya virus (CHIKV), nanopore sequencing allows rapid, culture-independent recovery of complete genomes from clinical and vector samples, enabling real-time tracking of viral diversity, evolution, and spread. Experiences from Ebola, Zika, and COVID-19 have demonstrated the power of portable sequencing, now applied to CHIKV monitoring. Advances in tools such as Guppy, Dorado, Minimap2, and Medaka enhance read quality, consensus accuracy, and downstream analyses. Despite challenges in basecalling and error correction, robust quality control pipelines ensure reliable results. Ongoing improvements in chemistry, flow cell design, and machine learning will further enhance fidelity and throughput, establishing nanopore sequencing as a cornerstone of CHIKV genomic surveillance and epidemic preparedness.

Chikungunya virus↗
PubMed1983

Defective interfering influenza RNAs of polymerase 3 gene contain single as well as multiple internal deletions.

Defective interfering (DI) RNAs of influenza virus arise from polymerase genes by internal deletions. Utilizing the recombinant DNA cloning and sequencing techniques we have determined the nucleotide sequence of two DI RNAs of L clone of A/WSN/33 (L2a-7 and L2a-17) which are of polymerase 3 origin. L2a-7 DI RNA is 659 nucleotides long and contains a single internal deletion of 1682 nucleotides (nucleotide position 273 to 1954) of P3 gene. L2a-17 DI RNA (611 nucleotides long), on the other hand, contains two internal deletions: one of 1682 nucleotides at the identical position as that in L2a-7, the other 48 nucleotides at the nucleotide position 2032 to 2079 of P3 gene. Except for a few base mismatches the sequence of DI RNAs are identical to the corresponding portion of the P3 gene including the 5' and the 3' termini. Since these two DI RNAs contain one identical deletion but differ in the other deletion as well as in base mismatches, these two DI RNAs appear to originate from a progenitor DI RNA rather than independently from the progenitor P3 gene. The sequences around the deletion point do not reflect a consensus sequence for the origin of these deletions and suggest the role of multiple mechanisms in the generation and evolution of influenza DI RNAs.

Base Sequence↗
PubMed1991

The nucleotide sequence of 3C proteinase region of the coxsackievirus A24 variant: comparison of the isolates in Taiwan in 1985-1988.

Acute hemorrhagic conjunctivitis caused by coxsackievirus A24 variant (CA24v) first appeared in Taiwan in October 1985, followed by two other sequential epidemics in 1986 and 1988. In order to know the evolutionary relationship of the CA24v strains isolated in Taiwan, we first determined the nucleotide sequence of the 3C proteinase (3Cpro) region of the prototype strain (EH24/70), isolated in Singapore in 1970, by molecular cloning. The nucleotide sequence of the 3Cpro region thus sequenced showed striking homology with polioviruses and coxsackievirus A21. Viral RNA of eight isolates obtained from the three epidemics was reverse transcribed, amplified by the polymerase chain reaction, and cloned into M13 phage for the production of ssDNA for nucleotide sequencing by the dideoxy chain termination method. When the number of nucleotide difference was taken as a genetic distance between isolates, all isolates showed a very similar distance from the EH24/70, the earliest isolate of CA24v, indicating that they evolved at a constant evolutionary rate. Phylogenetic analysis by the unweighted pairwise grouping method of arithmetic average (UPGMA) indicated that the six isolates collected in 1985 and 1986 were closely related, while two 1988 isolates were more distant from them. The branching time between these two groups was estimated to be May 1984, 18 months before the first recognition of the CA24v epidemic in Taiwan. This is the first report of the nucleotide sequence of CA24v genome RNA and of an evolutionary analysis of the virus using the nucleotide sequence.

3C Viral Proteases↗
PubMed1995

Mutations associated with viral sequences isolated from mice persistently infected with MHV-JHM.

Mouse hepatitis virus JHM (JHMV or MHV-4) induces subacute and chronic demyelination in rodents and has been studied as a model human demyelinating diseases, such a multiple sclerosis. However, despite intensive investigation, the state of JHMV during chronic disease is poorly understood. Using reverse transcription-polymerase chain reaction amplification (RT-PCR) to "rescue" viral RNA, we have found that JHMV-specific sequences persist for at least 787 days after intracerebral inoculation of experimental mice. Analysis of persisting viral RNA reveals that it is extensively mutated, and we hypothesize that the mutations observed reflect adaptation of the viral quasispecies to low-level intracellular replication during chronic disease.

Animals↗
PubMed1976

Endogenous C-type viruses: double agents in natural life processes.

C-type RNA viruses have been described in about 20 different vertebrate species. Their presence in man is suggested by electron microscopic, biochemical and serologic studies, although a definite re;icating human virus has not yet been isolated. These viruses are inherited through the germ cell and their production is regulated by genetic information carried in the host cell (i.e. endogenous virus). Two classes of endogenous C-type viruses have been recognized in certain animals particularly the mouse: ecotropic and xenotropic. They may have their counterparts in man. Ecotropic viruses spread through the host and can be easily transmitted to cells of the same species; they can produce malignancy. Xenotropic viruses cannot infect cells from their host species but are infectious for cells from heterologous species. The interaction between xenotropic and ecotropic viruses could lead to the transfer among species of genetic information relating to normal life processes and malignancy. These C-type viruses may play a role in evolution, normal development and differentiation as well as autoimmune disease and cancer.

Animals↗
PubMed1994

[Evolution of hepatitis C virus (HCV) viremia and adaptation of HCV in persistent infection in patients with acute hepatitis].

HCV viremia had ceased in majority of patients with acute resolving hepatitis C, and it continued for at least 1 year in all patients with chronicity. The HCV RNA titer in serum decreased markedly after the onset of acute hepatitis and then re-elevated in patients with chronicity. During this period, amino acid substitution rate in the E2/NS1 region (especially in HVR) was significantly higher in patients with acute hepatitis than in patients with chronic hepatitis. When patients with acute hepatitis C became persistent HCV carriers, the substitution rate decreased to the level seen in patients with chronic hepatitis. These observations suggest that rapid substitution of the amino acid sequence in the HVR of the E2/NS1 region may be one of the mechanisms of persistent HCV infection.

Acute Disease↗
PubMed1987

Geographic distribution of wild poliovirus type 1 genotypes.

Determination of the patterns of genomic variation among RNA virus isolates is a powerful approach for establishing their epidemiologic interrelationships. The standard technique for such studies, ribonuclease T1 oligonucleotide fingerprinting, can detect similarities only among very closely related isolates. The rapid evolution of the poliovirus genome during transmission in humans requires the application of alternate methods to identify more distant relationships. To obtain a substantially broader view of the distribution of wild poliovirus type 1 genotypes in nature, we compared 150 bases of genomic sequence information (encoding parts of the capsid protein VP1 and the noncapsid protein 2A) from 62 isolates obtained from poliomyelitis patients in five continents. The partial sequence information allowed us to (1) identify numerous geographic foci of endemic circulation of wild type 1 polioviruses, (2) reveal previously unsuspected links between cases in distant communities, (3) monitor the displacement from the environment of preexisting polioviruses by viruses from other regions, and (4) recognize the recombinant (vaccine-wild; wild-wild) origins of some epidemic polioviruses.

Base Sequence↗