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PubMed2004

Phylogenetic analysis of the full-length SARS-CoV sequences: evidence for phylogenetic discordance in three genomic regions.

The origin of the severe acute respiratory syndrome-coronavirus (SARS-CoV) remains unclear. Evidence based on Bayesian scanning plots and phylogenetic analysis using maximum likelihood (ML) and Bayesian methods indicates that SARS-CoV, for the largest part of the genome ( approximately 80%), is more closely related to Group II coronaviruses sequences, whereas in three regions in the ORF1ab gene it shows no apparent similarity to any of the previously characterized groups of coronaviruses. There is discordant phylogenetic clustering of SARS-CoV and coronaviruses sequences, throughout the genome, compatible with either ancient recombination events or altered evolutionary rates in different lineages, or a combination of both.

Evolution, Molecular↗
PubMed2006

Evolution of EV71 genogroup in Taiwan from 1998 to 2005: an emerging of subgenogroup C4 of EV71.

In Taiwan, enterovirus 71 (EV71) has played an important role in severe enterovirus-related cases every year since the devastating outbreak in 1998. Three genogroups A, B, C occur worldwide; with the B and C genogroups being subdivided into B1-B4 and C1-C4 subgenogroups respectively. To understand the mutation of the EV71 genogroup in Taiwan before and after 1998, a total of 54 worldwide strains were studied including 41 Taiwanese strains obtained in 1986 and 1998-2004. A fragment of 207 bp of the VP4 region was amplified and sequenced. Genetic analysis was performed using MEGA software (version 3.0) for the nucleotide sequence alignment and phylogenetic analysis. In Taiwan, the subgenogroup B1 was predominant before 1998 while subgenogroup C2 was the major etiologic group in 1998 outbreak. A minor etiologic group outbreak in 1998, subgenogroup B4, became predominant during the period from 1999 to 2003. In this study, subgenogroup C4 emerged and became predominant in 2004 in Taiwan. The nucleotide differences between B1 and C2, C2 and B4, B4 and C4 were 20%-26%, 19%-27%, 18%-22%, respectively. Nucleotide sequence alignment revealed 67 substitutions. Most of the substitutions (62/67) were silent mutations. This is the first report about the emergence of EV71 subgenogroup C4 in Taiwan.

Base Sequence↗
PubMed2025

Phylogenetic and Genetic Evolution Analysis of Complete SFTSV Genome Sequences in Shandong Province, China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV). Shandong province is one of the epidemic regions with high incidence rate of SFTS. To investigate phylogenetical and genetic evolution characteristics of SFTSV in Shandong province, we isolated SFTSV from suspected patients between April 2023 and October 2024, and then whole SFTSV genomes were amplified and sequenced in this study. A total of 25 new strains were analyzed together 56 strains submitted in Genbank from Shandong province. Phylogenetical and genetic analyses of the data set revealed that four genotypes were co-circulating in Shandong province. C3 genotype was the most common genotype in each year with lower genetic divergence. 298 amino acid substitutions were detected in the four proteins of SFTSV, but only two substitutions (Arg624Lys and Arg962Ser) had been proven to have potential impacts on biological functions. In addition, one reassortment strain (C3/C4/C4 for L, M and S segments) and three recombinant strains were identified. Analysis of selection pressure at the level of amino acid substitutions indicated genes within the four ORFs of SFTSV were all subjected to negative selection. In conclusion, the genetic characteristics and evolutionary mechanism of SFTSV was complex in Shandong province. It is necessary to conduct continuous surveillance to grasp the genetic evolution patterns, and to discover novel prevalent variants in a timely manner.

China↗
PubMed2025

Frequent Genomic Recombination in the 5'-Proximal Region Characterizes Human Adenovirus Species C Evolution.

To advance our understanding of the molecular recombination dynamics of circulating human adenovirus species C (HAdV-C) strains, whole genome sequence (WGS) analysis of seven strains representing five genotypes (P1H1F1, P1H2F2, P89H5F5, P2H2F2, and Px1/Ps3H1F1) isolated from pediatric severe acute respiratory infection (SARI) cases in China were performed, involving sequence similarity assessment, phylogenetic inference, and recombination mapping. The genomic analysis of seven strains showed substantial nucleotide identity (93.5%-99.2%) and distinct recombination patterns. Further comparative recombinant analysis with eight prototype strains and 214 publicly available strains revealed that strains with high genomic similarity or evolutionary relatedness showed substantial conservation in the posterior genomic regions, while the 5'-proximal ~14 000 bp region, particularly E1 and E2B regulatory and replication-associated genes, displayed significant recombination activity. In addition, identical or similar recombination patterns were found in the genomes of strains with high sequence identity and homology, which had been detected by different surveillance systems, and in multiple provinces in China and other countries. Further analysis revealed an independent evolutionary cluster for two strains (Henan2018-431 and Jilin2019-101), which also harbored fragments of unknown origin within the E3 region, potentially representing novel HAdV-C variants. These findings highlight the critical role of frequent recombination in HAdV-C evolution, particularly in low-diversity genomic regions, and emphasize the importance of WGS-based surveillance for tracking emerging recombinant strains with public health implications.

Humans↗
PubMed1987

Structure of an insect virus at 3.0 A resolution.

We report the first atomic resolution structure of an insect virus determined by single crystal X-ray diffraction. Black beetle virus has a bipartite RNA genome encapsulated in a single particle. The capsid contains 180 protomers arranged on a T = 3 surface lattice. The quaternary organization of the protomers is similar to that observed in the T = 3 plant virus structures. The protomers consist of a basic, crystallographically disordered amino terminus (64 residues), a beta-barrel as seen in other animal and plant virus subunits, an outer protrusion composed predominantly of beta-sheet and formed by three large insertions between strands of the barrel, and a carboxy terminal domain composed of two distorted helices lying inside the shell. The outer surfaces of quasi-threefold related protomers form trigonal pyramidyl protrusions. A cleavage site, located 44 residues from the carboxy terminus, lies within the central cavity of the protein shell. The structural motif observed in BBV (a shell composed of 180 eight-stranded antiparallel beta-barrels) is common to all nonsatellite spherical viruses whose structures have so far been solved. This highly conserved shell architecture suggests a common origin for the coat protein of spherical viruses, while the primitive genome structure of BBV suggests that this insect virus represents an early stage in the evolution of spherical viruses from cellular genes.

Biological Evolution↗
PubMed1997

Rapid evolution of translational control mechanisms in RNA genomes.

We have introduced 13 base substitutions into the coat protein gene of RNA bacteriophage MS2. The mutations, which are clustered ahead of the overlapping lysis cistron, do not change the amino acid sequence of the coat protein, but they disrupt a local hairpin, which is needed to control translation of the lysis gene. The mutations decreased the phage titer by four orders of magnitude but, upon passaging, the virus accumulated suppressor mutations that raised the fitness to almost wild-type level. Analysis of the pseudorevertants showed that the disruption of the local hairpin, controlling expression of the lysis gene, had apparently been so complete that its restoration by chance mutations could not be achieved. Instead, alternative foldings initiated by the starting mutations were further stabilized and optimized. Strikingly, in the pseudorevertants analyzed, translational control of the lysis gene had been restored. This feat was accomplished by, on average, four suppressor mutations that generally occurred at codon wobble positions. We also introduced 11 mutations in a hairpin more upstream in the coat protein gene and not implicated in lysis control. Here the titer dropped by three logs, but pseudorevertants with a fitness close to wild-type were soon generated. These pseudorevertants again were the result of the optimization of alternative foldings induced by the mutations. The transition of the secondary structure from wild-type to pseudorevertant could be visualized by structure probing. Our study shows that the folding of the RNA is an important phenotypic property of RNA viruses. However, its distortion can easily be overcome by optimizing alternative base-pairings. These new structures are not qualitatively equivalent to the original one, since they do not successfully compete with the wild-type.

Base Sequence↗
PubMed2000

Mutations induced by bacteriophage T7 RNA polymerase and their effects on the composition of the T7 genome.

We show here that transcription by the bacteriophage T7 RNA polymerase increases the deamination of cytosine bases in the non-transcribed strand to uracil, causing C to T mutations in that strand. Under optimal conditions, the mutation frequency increases about fivefold over background, and is similar to that seen with the Escherichia coli RNA polymerase. Further, we found that a mutant T7 RNA polymerase with a slower rate of elongation caused more cytosine deaminations than its wild-type parent. These results suggest that promoting cytosine deamination in the non-transcribed strand is a general property of transcription in E. coli and is dependent on the length of time the transcription bubble stays open during elongation. To see if transcription-induced mutations have influenced the evolution of bacteriophage T7, we analyzed its genome for a bias in base composition. Our analysis showed a significant excess of thymine over cytosine bases in the highly transcribed regions of the genome. Moreover, the average value of this bias correlated well with the levels of transcription of different genomic regions. Our results indicate that transcription-induced mutations have altered the composition of bacteriophage T7 genome and suggest that this may be a significant force in genome evolution.

Amination↗
PubMed2001

In silico structural and functional analysis of the human cytomegalovirus (HHV5) genome.

The open reading frames of human cytomegalovirus (human herpesvirus-5, HHV5) encode some 213 unique proteins with mostly unknown functions. Using the threading program, ProCeryon, we calculated possible matches between the amino acid sequences of these proteins and the Protein Data Bank library of three-dimensional structures. Thirty-six proteins were fully identified in terms of their structure and, often, function; 65 proteins were recognized as members of narrow structural/functional families (e.g. DNA-binding factors, cytokines, enzymes, signaling particles, cell surface receptors etc.); and 87 proteins were assigned to broad structural classes (e.g. all-beta, 3-layer-alphabetaalpha, multidomain, etc.). Genes encoding proteins with similar folds, or containing identical structural traits (extreme sequence length, runs of unstructured (Pro and/or Gly-rich) residues, transmembrane segments, etc.) often formed tandem clusters throughout the genome. In the course of this work, benchmarks on about 20 known folds were used to optimize adjustable parameters of threading calculations, i.e. gap penalty weights used in sequence/structure alignments; new scores obtained as simple combinations of existing scoring functions; and number of threading runs conducive to meaningful results. An introduction of summed, per-residue-normalized scores has been essential for discovery of subdomains (EGF-like, SH2, SH3) in longer protein sequences, such as the eight "open sandwich" cytokine domains, 60-70 amino acids long and having the 3beta1alpha fold with one or two disulfide bridges, present in otherwise unrelated proteins.

Amino Acid Sequence↗
PubMed2001

Nucleotide sequence of coliphage HK620 and the evolution of lambdoid phages.

HK620 is a temperate lambdoid bacteriophage that adsorbs to the O-antigen of its host, Escherichia coli H. The genome of a temperature-sensitive clear-plaque mutant consists of 38,297 nucleotides in which we recognize 60 open reading frames (orfs). Eighteen of these lie in a region of the genome that we call the virion structure domain. The other 42 orfs lie in what we call the metabolic domain. Virions of HK620 resemble those of phage P22. The virion structural orfs encode three kinds of putative proteins relative to the virion proteins of P22: (1) those that are nearly (about 90 %) identical; (2) those that are weakly (about 30 %) identical; and (3) those composed of nearly and weakly identical segments. We hypothesize that these composite proteins form bridges between the virion proteins of the other two kinds. Three of the putative virion proteins that are only weakly identical to P22 proteins are 71, 60 and 79 % identical to proteins encoded by the phage APSE-1, whose virions also resemble those of P22. Because the hosts of APSE-1 and HK620 have been separated from each other by an estimated 200 My, we propose using the amino acid differences that have accumulated in these proteins to estimate a biological clock for temperate lambdoid phages. The putative transcriptional regulatory gene circuitry of HK620 seems to resemble that of phage lambda. Integration, on the other hand, resembles that of satellite phage P4 in that the attP sequence lies between the leftward promoter and int rather than downstream of int. Comparing the metabolic domains of several lambdoid phage genomes reveals seven short conserved sequences roughly defining boundaries of functional modules. We propose that these boundary sequences are foci of genetic recombination that serve to assort the modules and make the metabolic domain highly mosaic genetically.

Attachment Sites, Microbiological↗
PubMed2002

The genome of bacteriophage phiKZ of Pseudomonas aeruginosa.

Bacteriophage phiKZ is a giant virus that efficiently infects Pseudomonas aeruginosa strains pathogenic to human and, therefore, it is attractive for phage therapy. We present here the complete phiKZ genome sequence and a preliminary analysis of its genome structure. The 280,334 bp genome is a linear, circularly permutated and terminally redundant, A+T-rich double-stranded DNA molecule. The phiKZ DNA has no detectable sequence homology to other viruses and microorganisms, and it does not contain NotI, PstI, SacI, SmaI, XhoI, and XmaIII endonuclease restriction sites. The genome has 306 open reading frames (ORFs) varying in size from 50 to 2237 amino acid residues. According to the orientation of transcription, ORFs are apparently organized into clusters and most have a clockwise direction. The phiKZ genome also encodes six tRNAs specific for Met (AUG), Asn (AAC), Asp (GAC), Leu (TTA), Thr (ACA), and Pro (CCA). A putative promoter sequence containing a TATATTAC block was identified. Most potential stem-loop transcription terminators contain the tetranucleotide UUCG loops. Some genes may be assigned as phage-encoded RNA polymerase subunits. Only 59 phiKZ gene products exhibit similarity to proteins of known function from a diversity of organisms. Most of these conserved gene products, such as dihydrofolate reductase, ribonucleoside diphosphate reductase, thymidylate synthase, thymidylate kinase, and deoxycytidine triphosphate deaminase are involved in nucleotide metabolism. However, no virus-encoded DNA polymerase, DNA replication-associated proteins, or single-stranded DNA-binding protein were found based on amino acid homology, and they may therefore be strongly divergent from known homologous proteins. Fifteen phiKZ gene products show homology to proteins of pathogenic organisms, including Mycobacterium tuberculosis, Haemophilus influenzae, Listeria sp., Rickettsia prowazakeri, and Vibrio cholerae that must be considered before using this phage as a therapeutic agent. The phiKZ coat contains at least 40 polypeptides, and several proteins are cleaved during virus assembly in a way similar to phage T4. Eleven phiKZ-encoded polypeptides are related to proteins of other bacteriphages that infect a variety of hosts. Among these are four gene products that contain a putative intron-encoded endonuclease harboring the H-N-H motif common to many double-stranded DNA phages. These observations provide evidence that phages infecting diverse hosts have had access to a common genetic pool. However, limited homology on the DNA and protein levels indicates that bacteriophage phiKZ represents an evolutionary distinctive branch of the Myoviridae family.

Amino Acid Sequence↗
PubMed2002

Bacteriophage Mu genome sequence: analysis and comparison with Mu-like prophages in Haemophilus, Neisseria and Deinococcus.

We report the complete 36,717 bp genome sequence of bacteriophage Mu and provide an analysis of the sequence, both with regard to the new genes and other genetic features revealed by the sequence itself and by a comparison to eight complete or nearly complete Mu-like prophage genomes found in the genomes of a diverse group of bacteria. The comparative studies confirm that members of the Mu-related family of phage genomes are genetically mosaic with respect to each other, as seen in other groups of phages such as the phage lambda-related group of phages of enteric hosts and the phage L5-related group of mycobacteriophages. Mu also possesses segments of similarity, typically gene-sized, to genomes of otherwise non-Mu-like phages. The comparisons show that some well-known features of the Mu genome, including the invertible segment encoding tail fiber sequences, are not present in most members of the Mu genome sequence family examined here, suggesting that their presence may be relatively volatile over evolutionary time. The head and tail-encoding structural genes of Mu have only very weak similarity to the corresponding genes of other well-studied phage types. However, these weak similarities, and in some cases biochemical data, can be used to establish tentative functional assignments for 12 of the head and tail genes. These assignments are strongly supported by the fact that the order of gene functions assigned in this way conforms to the strongly conserved order of head and tail genes established in a wide variety of other phages. We show that the Mu head assembly scaffolding protein is encoded by a gene nested in-frame within the C-terminal half of another gene that encodes the putative head maturation protease. This is reminiscent of the arrangement established for phage lambda.

Amino Acid Sequence↗
PubMed1996

Organization of the 3'-terminal half of beet yellow stunt virus genome and implications for the evolution of closteroviruses.

The 3'-terminal half of the beet yellow stunt virus (BYSV) genome 10,545 nt, has been cloned and sequenced. The sequenced portion of the BYSV genome encompasses 10 open reading frames (ORFs) and 241 nt of the 3' untranslated region. The sequence spans, in the 5' to 3' direction, the C-terminal region of the replication-associated polyprotein gene (ORF 1a) which includes the set of motifs typical of helicases (HEL), the entire 53-kDa polymerase (RdRp) gene (ORF 1b), and genes encoding 30-kDa (ORF 2), 6-kDa (ORF 3), 66-kDa (ORF 4), 61-kDa (ORF 5), 25-kDa (ORF 6), 23.7-kDa (coat protein, CP) (ORF 7), 18-kDa (ORF 8), and 22-kDa (ORF 9) proteins. The double-stranded RNA "replicative form" of the BYSV was demonstrated to have a nontemplate G residue at the 3' terminus of the (+) strand. The RdRp of BYSV is presumably expressed via a +1 ribosomal frameshift. The five-gene module conserved among closteroviruses was identified in BYSV; it includes a gene array coding for a 6-kDa small hydrophobic protein, a 66-kDa homolog of the cellular HSP70 heat shock proteins, a 61-kDa protein, and a 25-kDa diverged copy of the CP followed by the CP gene itself. Phylogenetic analysis of the replication-associated HEL and RdRp domains as well as proteins from the five-gene module demonstrated the closest relationship between BYSV and two other closteroviruses, beet yellows (BYV) and citrus tristeza (CTV) viruses. Like CTV, the BYSV genome contains a 30-kDa protein gene between the RdRp and the 6-kDa protein genes, and like BYV it has only two genes downstream of the CP gene. The organization of the BYSV genome appears to be intermediate between BYV and CTV, which suggests that these three viruses might represent three distinct but probably close stages in the closterovirus evolution.

Amino Acid Sequence↗
PubMed1997

The complete nucleotide sequence of the egg drop syndrome virus: an intermediate between mastadenoviruses and aviadenoviruses.

The complete nucleotide sequence of an avian adenovirus, the egg drop syndrome (EDS) virus, was determined. The total genome length is 33,213 nucleotides, resulting in a molecular weight of 21.9 x 10(6). The GC content is only 42.5%. Between map units 3.5 and 76.9, the distribution of open reading frames with homology to known genes is similar to that reported for other mammalian and avian adenoviruses. However, no homologies to adenovirus genes such as E1A, pIX, pV, and E3 could be found. Outside this region, several open reading frames were identified without any obvious homology to known adenovirus proteins. In the region organized similarly as other adenoviral genomes, most homologies were found to an ovine adenovirus (OAV strain 287). The highest level of amino acid identity was found for the hexon proteins of EDS and OAV. The virus-associated RNA (VA RNA) was identified thanks to the homology with the VA RNA of fowl adenovirus serotype 1 (FAV1). Similarities with FAV1 were also found in the fiber protein. Our results demonstrate that the avian EDS virus represents an intermediate between mammalian and avian adenoviruses. The nucleotide sequence and genomic organization of the EDS virus reflect the heterogeneity of the aviadenovirus genus and the Adenoviridae family.

Adenoviridae↗
PubMed1998

Asymmetric infectivity of pseudorecombinants of cabbage leaf curl virus and squash leaf curl virus: implications for bipartite geminivirus evolution and movement.

The bipartite geminiviruses squash leaf curl virus (SqLCV) and cabbage leaf curl virus (CLCV) have distinct host ranges. SqLCV infects a broad range of plants within the Cucurbitaceae, including pumpkin and squash, and CLCV has a broad host range within Brassicaceae that includes cabbage and Arabidopsis thaliana. Despite this, the genomic A components of these viruses share a high degree of sequence identity, particularly in the gene encoding the replication protein AL1, and their common regions are 77% identical. However, there is unexpected sequence diversity in the common regions of the two CLCV genomic A and B components, these being only 80% identical. Based on these sequence similarities, we investigated the host range properties of pseudorecombinants of SqLCV and CLCV. We found that in a pseudorecombinant virus consisting of the A component of CLCV and the B component of SqLCV, both components replicated in tobacco protoplasts, and this pseudorecombinant was infectious and caused systemic disease in Nicotiana benthamiana, a common host to all bipartite geminiviruses. However, this pseudorecombinant did not move systemically in pumpkin or Arabidopsis, despite the demonstrated replication compatibility of the genome components. As a result of the greater sequence differences between the common regions, the pseudorecombinant of SqLCV A and CLCV B components neither replicated the CLCV B component nor systemically infected any of the hosts tested. These findings demonstrate that for different geminiviruses with distinct host ranges, the replication origins and AL1 proteins can be sufficiently similar to permit infectious pseudorecombinants, but replication alone is not sufficient to cause systemic disease, and host range may ultimately be limited at the level of movement. The results of this study further suggest that CLCV is an evolving virus that can provide insights into how new bipartite geminiviruses arise from mixed infections.

Base Sequence↗
PubMed1998

Evolutionary inferences of novel simian T lymphotropic virus type 1 from wild-caught chacma (Papio ursinus) and olive baboons (Papio anubis).

A serological survey of 22 wild-caught South African (Transvaal) chacma baboons (Papio ursinus) and eight olive baboons (Papio anubis) from Kenya indicates that 13 P. ursinus and one P. anubis have antibodies reacting with human T cell leukemia/lymphoma virus type 1 (HTLV-1) antigens, whereas three P. ursinus had a indeterminate reactivity on Western blot analysis. With six primer sets specific to either HTLV-1-Simian T-cell leukemia virus type 1 (STLV-1) or HTLV-2 and encompassing long terminal repeat (LTR), gag, pol, env, and tax sequences, polymerase chain reaction was performed on genomic DNA from peripheral blood mononuclear cells of 18 animals, and the presence of HTLV-1-STLV-1-related viruses was determined in 13 seropositive and three seroindeterminate animals but not in the two HTLV seronegative individuals. Proviral DNA sequences from env (522 bp), pol (120 bp), and complete (755 bp) or partial (514 bp) LTR were determined for three STLV-1-infected P. ursinus and one P. anubis. Comparative and phylogenetic analyses revealed that P. anubis (Pan-486) sequence clusters with one (Pan-1621) of two previously described P. anubis STLV-1. Likewise, P. ursinus viruses (Pur-529, Pur-539, and Pur-543) form a distinct group, different from all known HTLV-1 but closely affiliated with two STLV-1 strains from South African vervets (Cercopithecus aethiops pygerythrus). This study, reporting the first STLV-1 sequences from wild-caught P. ursinus and P. anubis, corroborates the hypothesis of cross-species transmissions of STLV-1 in the wild. Further, phylogenetic analyses indicate that the known HTLV-1 strains do not share a common origin with nonhuman primates STLV in South Africa.

Animals↗
PubMed1998

Coinfection of a fungal pathogen by two distinct double-stranded RNA viruses.

Unsegmented double-stranded (ds)RNA viruses belonging to the family Totiviridae persistently infect protozoa and fungi. In this study, two totiviruses were found to coinfect the filamentous fungus Sphaeropsis sapinea, a well known pathogen of pines. Isometric, virus-like particles approximately 35 nm in diameter were isolated from extracts of this fungus. The nucleotide sequences of the genomes of the two S. sapinea RNA viruses named SsRV1 and SsRV2 were established. The linear genomes of 5163 and 5202 bp, respectively, are identically organized with two large, overlapping ORFs. The 5' located ORF1 probably encodes the coat protein, whereas the gene product of ORF2 shows the typical features of RNA-dependent RNA polymerases. The absence of a pseudoknot and a slippery site at the overlapping region between ORF1 and ORF2, as well as the shortness of that region, leads us to suggest that the translation of ORF2 of both viruses is internally initiated. The mode of translation and the genomic organization are similar to those of Helminthosporium victoriae 190S virus (Hv190SV; Huang, S., and Ghabrial, S. A. (1996). Proc. Natl. Acad. Sci. USA 93, 12541-12546). Hv190SV thus appears to be closely related to the SsRVs. Interestingly, based on amino acid sequence homology SsRV1 is more closely related to Hv190SV than to SsRV2.

Amino Acid Sequence↗
PubMed1999

Pathogenicity and comparative evolution in vivo of the transitional quasispecies SIVsmmPBj8.

During 14 months of infection of a pig-tailed macaque, the acutely lethal simian immunodeficiency virus SIVsmmPBj14 (SIV-PBj14) evolved from the minimally pathogenic strain SIVsmm9. The virus isolated at 8 months (SIV-PBj8) exhibited properties of both SIVsmm9 and SIV-PBj14, indicating that a phenotypic transition occurred between 6 and 10 months. To assess the influence that this new composition of biologic properties might have on pathogenicity, three pig-tailed macaques were inoculated intravenously with SIV-PBj8. Although no animals developed the severe acute disease syndrome typical of SIV-PBj14, all had high levels of viremia and died of AIDS at 4, 10. 5, and 32 months. Characterization of the SIV-PBj8-derived quasispecies that evolved in these macaques showed that at 4 days after inoculation, viruses from all three animals exhibited in vitro properties different from those of the inoculum. By 4 months, the initial phenotypic profiles had changed, with the quasispecies in plasma from the animal (J90232) that died at this time most closely resembling SIV-PBj14, not SIV-PBj8. Phylogenetic trees of the gp41/Nef region of viruses in 4-month plasma from J90232 revealed three distinct populations with high bootstrap values: one group branched with SIVsmm9, one with SIV-PBj14, and one with SIV-PBj8 (ratio of clones, 5:9:5). Nucleotide sequence analysis suggested that some members of the original SIV-PBj8 quasispecies may have been evolving toward a SIV-PBj14-like genotype at the time macaque J90232 died. The use of SIV-PBj8, which was more pathogenic than SIVsmm9, but less pathogenic than SIV-PBj14, may provide the optimal genetic background on which to identify the minimal, multigenic determinants of the SIV-PBj14 phenotype. The results of our studies on SIV-PBj14 indicate that in some, but not all, cases of primate lentivirus infection more pathogenic variants evolve, selectively proliferate, and more than likely contribute to disease progression.

Animals↗
PubMed1999

Extensive sequence divergence and phylogenetic relationships between the fusogenic and nonfusogenic orthoreoviruses: a species proposal.

The orthoreoviruses can be divided into subgroups based on either their restricted host range or the unusual ability of certain members of this group of nonenveloped viruses to induce cell-cell fusion from within. Phylogenetic relationships cannot be inferred based on these biological properties because fusogenic reoviruses are present in both the avian and mammalian subgroups. To address this issue, the complete nucleotide sequences of the three S-class genome segments encoding the major sigma-class core, outer capsid, and nonstructural proteins of four fusogenic reoviruses were determined and used to establish the phylogeny of the orthoreoviruses. The viruses analysed included two strains of avian reovirus and the only known fusogenic mammalian reoviruses, Nelson Bay virus and baboon reovirus. Comparative sequence analysis of these fusogenic reoviruses and the prototypical nonfusogenic mammalian reoviruses indicated a highly diverged genus with both conserved and unique sequence-predicted structural motifs in the major sigma-class proteins. Phylogenetic analysis provided the basis for the first taxonomic subdivision of the orthoreoviruses into species classes based on inferred evolutionary relationships. It is proposed that the orthoreoviruses consist of at least four species that separate into three clades. The nonfusogenic mammalian reovirus species represent a single clade, and the fusogenic reoviruses separate into two distinct clades. The first clade of fusogenic reoviruses contains the avian reovirus- and Nelson Bay virus-type species, with the second clade being occupied by the single baboon reovirus isolate that represents a fourth orthoreovirus species.

Amino Acid Sequence↗