RESUMO
One subset of sequences present within mammalian genomes is the retroelements, which include endogenous retroviruses and retrotransposons. While there are typically thousands of copies of endogenous retroviruses within mammalian hosts, almost no LTR-retrotransposon-like sequences have been identified. Here, we report the presence of a remarkably intact and conserved gypsy-type LTR-retrotransposon sequence within the genomes of several mammals, including humans and mice. Each host probably contains a single orthologous element, indicating that the original, ancestral gypsy LTR-retrotransposon first integrated into mammals over 70 million years ago. It is thus the first described example of a near-intact orthologous retroelement within humans and mice and is one of the most ancient retroelement sequences described to date. Despite their extreme age, the orthologs within each species examined contain a large ORF, between 4.0 and 5.2 kb in length, encoding proteins with sequence similarity to LTR-retrotransposon-derived Capsid (CA), Protease (PR), Reverse Transcriptase (RT), RibonucleaseH (RNaseH), and Integrase (IN). Calculation of nonsynonymous and synonymous nucleotide substitution frequencies indicated that the encoded proteins are under purifying selection, suggesting that these elements have, in fact, been co-opted by their hosts. A possible function for these elements, involving gypsy LTR-retrotransposon restriction in mammals, is discussed.
Assuntos
Evolução Molecular , Mamíferos/genética , Filogenia , Retroelementos/genética , Sequências Repetidas Terminais/genética , Sequência de Aminoácidos , Animais , Mapeamento Cromossômico , Genoma , Humanos , Camundongos/genética , Dados de Sequência Molecular , Ratos/genética , Seleção Genética , Alinhamento de Sequência , Homologia de SequênciaRESUMO
Endogenous retroviruses (ERVs) are widespread in vertebrate genomes and have been loosely grouped into "classes" on the basis of their phylogenetic relatedness to the established genera of exogenous retroviruses. Four of these genera-the lentiviruses, alpharetroviruses, betaretroviruses, and deltaretroviruses-form a well-supported clade in retroviral phylogenies, and ERVs that group with these genera have been termed class II ERVs. We used PCR amplification and sequencing of retroviral fragments from more than 130 vertebrate taxa to investigate the evolution of the class II retroviruses in detail. We confirm that class II retroviruses are largely confined to mammalian and avian hosts and provide evidence for a major novel group of avian retroviruses, and we identify additional members of both the alpha- and the betaretrovirus genera. Phylogenetic analyses demonstrated that the avian and mammalian viruses form distinct monophyletic groups, implying that interclass transmission has occurred only rarely during the evolution of the class II retroviruses. In contrast to previous reports, the lentiviruses clustered as sister taxa to several endogenous retroviruses derived from rodents and insectivores. This topology was further supported by the shared loss of both the class II PR-Pol frameshift site and the class II retrovirus G-patch domain.
Assuntos
Retrovirus Endógenos/classificação , Genoma Viral , Animais , Evolução Biológica , Retrovirus Endógenos/genética , Lentivirus/genética , Dados de Sequência Molecular , Vertebrados/virologiaRESUMO
Replication of HIV-1 and N-tropic murine leukemia virus (N-MLV) is restricted in a number of different primate cells. In some cell lines, cross-saturation experiments suggest that the two viruses are interacting with the same restriction factor. Recently, Trim5alpha protein from rhesus monkey was found to restrict HIV-1. We have confirmed this result and have shown that Trim5alpha from two African green monkey cell lines, Vero and CV-1, also restricts HIV-1. In addition, we show that human, rhesus, and African green monkey Trim5alpha can restrict N-MLV. By using a panel of MLV capsid mutants, subtle differences in the anti-MLV activity were identified among the different primate Trim5alpha cDNAs. Trim1 isolated from humans and green monkeys was also found to restrict N-MLV. We hypothesize that the Trim family of proteins plays a widespread role in innate immunity to viral infection.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte/metabolismo , HIV-1/fisiologia , Vírus da Leucemia Murina/fisiologia , Proteínas/metabolismo , Replicação Viral , Sequência de Aminoácidos , Animais , Fatores de Restrição Antivirais , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Proteínas de Transporte/genética , Linhagem Celular , Chlorocebus aethiops , Humanos , Macaca mulatta , Proteínas de Membrana/metabolismo , Camundongos , Dados de Sequência Molecular , Proteínas/química , Proteínas/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Proteínas com Motivo Tripartido , Ubiquitina-Proteína LigasesRESUMO
Lv1 restriction of HIV-1 in the cells of Old World monkeys is associated with the expression of the Trim5 gene. Uniquely, in owl monkey kidney cells, HIV-1 restriction is dependent on the ability of incoming viral capsid protein to bind cyclophilin A (CypA). Cloning of the owl monkey Trim5 gene now reveals the presence of an inserted CypA pseudogene within intron 7 of the Trim5 gene. This insertion results in the formation of a chimeric Trim5-CypA transcript. Transfer of a cDNA corresponding to this transcript into human cells confers cyclosporin A-sensitive resistance to HIV-1 infection. The restriction factor appears to be a chimeric protein created by retrotransposon-mediated exon shuffling.