京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18897号 / 医博第4008号 / 新制||医||1009(附属図書館) / 31848 / 京都大学大学院医学研究科医学専攻 / (主査)教授 松岡 雅雄, 教授 朝長 啓造, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Recent discoveries indicate that the foamy virus (FV) (Spumavirus) ancestor may have been among the first retroviruses to appear during the evolution of vertebrates, demonstrated by foamy endogenous retroviruses present within deeply divergent hosts including mammals, coelacanth, and ray-finned fish. If they indeed existed in ancient marine environments hundreds of millions of years ago, significant undiscovered diversity of foamy-like endogenous retroviruses might be present in fish genomes. By screening published genomes and by applying PCR-based assays of preserved tissues, we discovered 23 novel foamy-like elements in teleost hosts. These viruses form a robust, reciprocally monophyletic sister clade with sarcopterygian host FV, with class III mammal endogenous retroviruses being the sister group to both clades. Some of these foamy-like retroviruses have larger genomes than any known retrovirus, exogenous or endogenous, due to unusually long gag-like genes and numerous accessory genes. The presence of genetic features conserved between mammalian FV and these novel retroviruses attests to a foamy-like replication biology conserved for hundreds of millions of years. We estimate that some of these viruses integrated recently into host genomes; exogenous forms of these viruses may still circulate.

Endogenous retroviruses (ERVs) are fossils of ancient retroviral infection in the germline. In primates they represent around 5% of the genome sequence. During time spent in the genome, being transmitted in a Mendelian fashion, copies of ERVs have accumulated mutations, which rendered them inactive. However, some of them (the most recently integrated ones) are still able to transcribe and produce viral proteins, although few are capable of re-infection. In the past often considered as unharmful 'junk DNA', recent evidence link ERVs with cancer and several inflammatory diseases. For example, a few reports demonstrate that ERVs are involved in tumour development using shRNA knock-down and over-expression systems, and their overexpression tends to correlate with inflammation status, generating the hypothesis that they can act as pathogen-associated molecular patterns (PAMPs) and bind to innate sensors. Focusing on the Human (Homo sapiens) and the rhesus macaque (Macaca mulatta), the main aims of this thesis are to look for further evidence linking ERVs to tumour development, with possible implications for therapies, and test the hypothesis that ERVs are PAMPs by seeing if individuals with higher levels of ERV expression exhibit a higher innate immune response. The work on ERVs in cancer involved the human ERV type-K HML2 lineage (HERV-K (HML2)), an ERV lineage found in humans, in Merlin-deficient tumours. These are schwannomas that arise from Schwann cells and for which effective drug therapy is urgently needed. The work on ERVs in inflammation involved the Papio cynocephalus ERV (PcEV), in rhesus macaques infected with simian immunodeficiency virus (SIV) infection. The main outcomes are as follows: regarding HERV-K (HML2) in human schwannomas, (i) HERV-K (HML2) proteins are overexpressed in schwannoma compared to Schwann cells; (ii) these proteins are released from the tumour; (iii) regulation of HERV-K (HML2) expression in the tumour appears to involve the transcription factor TEAD; (iv) schwannomas are potentially treatable using anti-HERV-K (HML2) monoclonal antibodies and antiretroviral drugs since both decreased proliferation in vitro. Regarding PcEV in SIV-infected macaques: (i) PcEV is transcriptionally active; (ii) PcEV can be retrieved at low levels in the blood of some macaque animals; (iii) the levels of PcEV in cells correlates strongly with the strength of the innate response as measured by cellular levels of STAT1 transcripts - an interferon-stimulated gene (ISG). Other recent research has shown that human ERV lineages, namely HERV-W and HERV-H, have been co-opted and are involved in placentation and pluripotency during development, respectively. The present work suggests that ERVs are involved in a wide range of biological process and supports the need for further research into the biological significance of ERVs for their hosts.

Long terminal repeat (LTR) retrotransposons are autonomous eukaryotic repetitive elements which may elicit prolonged genomic and immunological stress on their host organism. LTR retrotransposons comprise approximately 10 % of the mammalian genome, but previous work identified only 1.35 % of the chicken genome as LTR retrotransposon sequence. This deficit appears inconsistent across birds, as studied Neoaves have contents comparable with mammals, although all birds contain only one LTR retrotransposon class: endogenous retroviruses (ERVs). One group of chicken-specific ERVs (Avian Leukosis Virus subgroup E; ALVEs) remain active and have been linked to commercially detrimental phenotypes, such as reduced lifetime egg count, but their full diversity and range of phenotypic effects are poorly understood. A novel identification pipeline, LocaTR, was developed to identify LTR retrotransposon sequences in the chicken genome. This enabled the annotation of 3.01 % of the genome, including 1,073 structurally intact elements with replicative potential. Elements were depleted within coding regions, and over 40 % of intact elements were found in clusters in gene sparse, poorly recombining regions. RNAseq analysis showed that elements were generally not expressed, but intact transcripts were identified in four cases, supporting the potential for viral recombination and retrotransposition of non-autonomous repeats. LocaTR analysis of seventy-two additional sauropsid genomes revealed highly lineage-specific repeat content, and did not support the proposed deficit in Galliformes. A second, novel bioinformatic pipeline was constructed to identify ALVE insertions in whole genome resequencing data and was applied to eight elite layer lines from Hy-Line International. Twenty ALVEs were identified and diagnostic assays were developed to validate the bioinformatic approach. Each ALVE was sequenced and characterised, with many exhibiting high structural intactness. In addition, a K locus revertant line was identified due to the unexpected presence of ALVE21, confirmed using BioNano optic maps. The ALVE identification pipeline was then applied to ninety chicken lines and 322 different ALVEs were identified, 81 % of which were novel. Overall, broilers and non-commercial chickens had a greater number of ALVEs than were found in layers. Taken together, these two analyses have enabled a thorough characterisation of both the abundance and diversity of chicken ERVs.

Thesis advisor: Welkin E. Johnson / Endogenous retroviruses (ERVs) make up a significant portion of vertebrate genomes, and serve as a fossil record of past retroviral infections. Although most ERV genes acquire inactivating mutations over time, some loci retain open reading frames (ORFs) across one or more of the viral genes. The ERV-Fc family, for example, endogenized in multiple mammalian hosts 10 to 30 million years ago, yet many copies maintain intact ORFs corresponding to the env gene, including loci in humans (HERV-Fc1-env) and baboons (babERV-Fc2-env). We previously identified intact ERV-Fc-related env sequences in eight additional mammalian species: chimpanzee, bonobo, aardvark, grey mouse lemur, squirrel monkey, marmoset, dog, and panda. Here we present the results of our assays of expression of these full-length Env proteins. We found that most of the precursors were not cleaved to form the functional surface (SU) and transmembrane (TM) subunits, even when a canonical furin cleavage site was still intact. An exception was babERV-Fc2, in which reconstruction of the cleavage site led to cleavage into SU and TM subunits. Furthermore, removal of 22 residues from the C-terminus of the cytoplasmic tail of babERV-Fc2 enhanced syncytia formation and the ability of babERV-Fc2 pseudotyped virions to infect 293T cells, suggesting the presence of an R-peptide cleavage mechanism. A survey of a small panel of cells revealed that only human cell lines were infectable by babERV-Fc2 pseudotyped murine leukemia virus (MLV) particles, whereas cells of old world monkey, canine, feline and chicken origin were not susceptible to infection. Ectopic expression of native Env codon optimized babERV-Fc2 Env can also inhibit infection by reconstructed babERV-Fc2 pseudotyped virus, raising the possibility that the endogenous glycoprotein encoded in the baboon genome may function as a viral entry inhibitor. Our results suggest that exaptation of ERV Env proteins as antiviral defense genes involves a combination of selective pressures: selection to preserve the receptor-binding and receptor interference functions of Env, but also selection to eliminate the membrane fusion related functions. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

No description available.

Thesis advisor: Welkin Johnson / Endogenous Retroviruses (ERVs) are “fossilized” retroviruses of a once exogenous retrovirus located in the genome of extant vertebrates. Retroviral infection results in a provirus integration into the host genome. An infection of a germline cell could lead to the provirus potentially being inherited by the offspring of the infected individual. Once in the genome, the provirus becomes subject to evolutionary processes and can become either lost or fixed in a population, remaining as “fossils” long after the exogenous retrovirus has gone extinct23. Notably, 8% of the human genome consists of ERVs30. Human Endogenous Retrovirus Type K (HERV-K)(HML-2) family is of particular interest. HERV-K integrations are as old as 30-35 million years, endogenizing before the separation of humans and Old World Monkeys. However, there are human specific insertions, some as young as 150,000 – 250,000 years, making them the youngest insertion in the human genome. There are over 90 insertions in the human genome; the bulk is shared by all humans44,47. Transcripts of HERV-K genes are upregulated in multiple cancer and tumor cell lines 14,39,46, as well as in HIV-1 infected patients 7,11,29. Just as there are human specific insertions of ERV-K, there are also Old World Monkey specific insertions44. I have identified an intact endogenous retroviral envelope open reading frame on chromosome 12 of the rhesus macaque genome. This viral envelope-encoding sequence, which I refer to as rhERV-K env, retains all the canonical features of a retroviral Env protein. An alignment between rhERV-K env and a consensus sequence of HERV-K, HERV-Kcon env, shows a 70% amino acid sequence identity. For experimental purposes, reconstructed HERV-K envelopes have been incorporated into virions of Human Immunodeficiency virus (HIV-1)19,26,49, Murine Leukemia Virus (MLV)12, and Vesicular stomatitis Virus (VSV)26,41,49. While these approaches have illuminated some aspects of HERV-K Env-mediated entry, to date a cell-surface receptor has not been identified for any ERV-K Env. This could be due to its low infectivity levels12,26,49, its seemingly broad cell tropism limiting identification of null cell lines26,49, or possibly the HERV-K consensus reconstructions are not an accurate representation of the progenitor HERV-K virus. I am interested in understanding how the ERV-K retrovirus accessed the human germline (some 150,000 – 250,000 years ago). To do this, I focused specifically on the envelope proteins of HERV-K and rhERV-K, with the goal of analyzing the ERV-K entry process. The identification and inclusion of rhERV-K Env in this study is meant to circumvent the possibility that the previously described consensus reconstructions of human HERV-K Env are not representative, and may also provide a means to compare the endogenization process in the human/ape and old-world monkey lineages. I focused on developing two systems for single-cycle infection, one based on Mason-Pfizer Monkey Virus (MPMV) (which has not been done before), and a second based on MLV, which has previously been reported on. MPMV, like HERV-K, is a betaretrovirus, and I reasoned that possibly using a betaretrovirus would overcome some of the low-infectivity issues associated with prior attempts using HIV and MLV. To develop a system for examining function of the ERV-K Env proteins, I addressed 3 issues: 1. Are the HERV-K Env and rhERV-K Env proteins expressed and properly processed? 2. Can they be incorporated into virions of a heterologous virus? 3. Are ERV-K pseudotyped virions infectious? I have answered these questions in the following thesis. / Thesis (MS) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

La domestication des bétails représente une étape importante dans l'histoire de l'humanité. Le mouton était l'un des premiers animaux à être domestiqués dans le croissant fertile. Ces événements de domestication, probablement initiés au début du Néolithique, ont génétiquement construit les races contemporaines du Moyen-Orient mais aussi du monde entier. L'élevage de moutons, principalement mouton de la race Awassi, représente une activité économique essentielle du Liban ; cependant, jusqu'à présent, il n'existe que très peu de données génétiques sur cette race. De nos jours, les outils moléculaires disponibles nous permettent de définir en détail la diversité génétique des populations de moutons et de retracer leur histoire évolutive. Par conséquent, l'objectif principal de mon projet de thèse était de caractériser génétiquement la race Awassi du Liban. Pour cette étude, 277 échantillons d'ADN génomique prélevés des moutons Awassi du Liban (n = 254) et de la Syrie (n = 23) ont été analysés. Au début, nous avons utilisé cinq rétrovirus endogènes (rétrovirus endogène de moutons de Jaagsiekte-enJSRV) qui sont polymorphiques par insertion dans les génomes du mouton domestique (enJSRV-18, -7, -15, -16 et -22) et ont été précédemment considérés comme très informatifs principalement pour distinguer génétiquement les moutons primitifs des races plus modernes (c.-à-d. le dernier issu de l'épisode migratoire impliquant des moutons avec des traits de production améliorés). En utilisant cette approche, nos résultats montrent une prédominance du type R2 (enjSRV-18 seulement) confirmant que le mouton Awassi du Liban est une race moderne. Comme prévu, le rétrotype R4 (à la fois enJSRV-18 et enJSRV-7), une caractéristique commune des populations de moutons du bassin méditerranéen, se trouve également dans le génome des moutons d'Awassi du Liban et plus accentué dans les troupeaux Syriens. Il est intéressant de noter que les populations de moutons d'Awassi situés dans le nord-est du Liban et ayant ainsi un accès plus restreint à la mer Méditerranée que les autres populations (c'est-à-dire en raison de la chaîne de montagne centrale qui coupe le pays sur deux), présentent une faible fréquence de R4. Bien que l'origine des animaux utilisés pour établir les troupeaux analysés au cours de cette étude soit inconnue, nos résultats fournissent également certaines preuves que le mode d'élevage (ouvert ou fermé) peut influencer les rétrotypes observés et en particulier le R4. De manière surprenante, au cours de cette étude, nous avons également dévoilé la présence de soi-disant "Solo-LTR" (c'est-à-dire généré par une recombinaison homologue) pour un autre enJSRV (enJSRV-6) qui prédomine dans deux troupeaux d'une région particulière du Liban (Nabatieh). Et comme approche complémentaire, deux marqueurs mitochondriaux ont été utilisés, le cytochrome b (Cyt-b) et D-Loop, pour étudier l'origine maternelle de cette race et sa relation phylogénétique au sein de la famille Ovis aries. Dans notre étude, le Cyt-b se révèle plus discriminant que le D-Loop. Des mouton d'Awassi analysé, quatre haplogroupes (HPG) du Moyen-Orient ont été trouvés avec l'analyse du Cyt-b : HPG A, B, C et E, ce dernier étant peu fréquent. De même, l’analyse de la super-séquence, alignement Cyt-b_D-Loop, a permis l’identification de l’HPG D, un HPG extrêmement rare et limité jusqu’à présent aux moutons à queue grasse tel que l’Awassi. Enfin, une expansion passée de la population est observée pour les HPG A, B et C (mais pas pour HPG E) avec les distributions incompatibles et des tests de neutralité négatifs significatifs. Dans l'ensemble, les résultats obtenus au cours de cette étude fournissent une caractérisation génétique complète ainsi que quelques idées sur la structure phylogéographique des populations de moutons de la race Awassi au Liban. / Livestock domestication represents a milestone in the history of mankind. Sheep was one of the first animals to be domesticated in the Fertile Crescent. These domestication events, probably initiated in the early Neolithic, have genetically built the contemporary races of the Middle East but also of the whole world. Sheep farming, mainly sheep of Awassi breed, represents an essential economic activity of Lebanon; however, so far, only very few genetic data exist on this breed. Nowadays, the molecular tools available allow us to define in details the genetic diversity of sheep populations and to trace their evolutionary history. Hence, the main objective of my PhD project was to genetically characterize the Awassi breed of Lebanon. For this study, 277 genomic DNA samples collected from Awassi sheep of Lebanon (n=254) and Syria (n=23) were analyzed. Initially, we used five endogenous retroviruses (endogenous Jaagsiekte sheep retrovirus-enJSRV) that are insertionally polymorphic within the genomes of domestic sheep (enJSRV-18, -7, -15, -16 and -22) and have been previously shown to be very informative mainly to genetically distinguish between primitive sheep from more modern breeds (i.e. the latter originating from the migratory episode involving sheep with improved production traits). Using this approach, our results show a predominance of the R2 retrotype (enJSRV-18 only) confirming that the Awassi sheep of Lebanon is a modern breed. As expected, the R4 retrotype (both enJSRV-18 and enJSRV-7), a common feature of the sheep populations present within the Mediterranean area, is also found in the Awassi sheep of Lebanon and to more extend in those of Syria. Interesting, the populations of Awassi sheep located in the northeast of Lebanon and thus having a more restricted access to the Mediterranean Sea than the other populations (i.e. due to the central mountain chain cutting the country in two) present R4 weaklier. Even though the origin of the animals used to establish the herds analyzed during this study is unknown, our results also provide some evidences that the mode of rearing (open or closed) may influence the observed retrotypes and in particular R4. Surprisingly, during this study, we also unveiled the presence of so-called “Solo-LTR” (i.e. generated by homologous recombination) for another enJSRV (enJSRV-6) that are predominant in two herds of a particular region of Lebanon (Nabatieh). As a complementary approach, two mitochondrial markers were used, the cytochrome b (Cyt-b) and D-Loop, to investigate the maternal origin of this breed and its phylogenetic relationship within the Ovis aries family. In our study, the Cyt-b turns out to be more discriminative than the D-Loop. From the Awassi sheep analyzed, four haplogroups (HPGs) of the Middle-East were found with Cyt-b analysis: HPG A, B, C and E, the latter being the least frequent. Also, the super-sequence analysis, Cyt-b_D-Loop alignment, allowed the identification of HPG D, an extremely rare HPG, limited till now to fat-tailed sheep such as Awassi. Finally, a past population expansion is observed for the HPG A, B and C (but not for HPG E) with mismatch distributions and significant negative neutrality tests. Overall, the results obtained during this study provide a comprehensive genetic characterization as well as some insights into the phylogeographic structure of the sheep populations of the Awassi breed in Lebanon.

Retrovírus endógenos (ERVs) são vírus altamente difundidos no genoma de vertebrados. ERVs surgem quando retrovírus exógenos infectam células germinativas e se disseminam no genoma de seus hospedeiros, transmitindo seu material genético através das gerações por meio de herança mendeliana. ERVs são fundamentais na evolução dos genomas, sendo eles responsáveis por uma parte da diversidade genética de seus hospedeiros. O conhecimento sobre ERVs na família Felidae (Mammalia, Carnivora) estava praticamente restrito ao gato doméstico, e não se conhecia diversidade e padrões de evolução desses retroelementos em outras espécies. Este estudo teve como objetivo investigar diversidade, distribuição e padrões evolutivos de ERVs em espécies de gatos silvestres. Utilizando ferramentas de biologia molecular e bioinformática, foram identificadas e caracterizadas 85 sequências similares a retrovírus endógenos nos representantes das oito espécies brasileiras: Leopardus pardalis, L. wiedii, L. colocolo, L. geoffroyi, L. tigrinus, Puma concolor, P. yagouaroundi e Panthera onca. Encontrou-se uma predominância de ERVs similares a Gammaretrovirus, um padrão característico em muitas espécies de mamíferos. As análises filogenéticas evidenciaram três grupos principais de Gammaretrovirus, cada um evoluindo de maneira peculiar. Em uma visão geral, os ERVs provenientes de diferentes hospedeiros apresentaram-se distribuídos de forma heterogênea nas filogenias, dificultando a constatação de um padrão coevolutivo. No entanto, análises mais detalhadas de algumas sequências demonstraram peculiaridades, como no caso de um grupo de sequências similares a de um ERV oriundo do morcego Myotis lucifugus. Através de análises filogenéticas em comparação com dados obtidos na literatura, sugere-se que a infecção desse retrovírus ocorreu em uma espécie ancestral de felídeo, na segunda metade do Mioceno. Os resultados obtidos permitiram demonstrar que os felídeos neotropicais apresentam ERVs que seguem padrões semelhantes aos descritos a respeito de outros mamíferos, sugerindo também alguns casos de infecções de retrovírus muito similares entre diferentes ordens de mamíferos. / Endogenous retroviruses (ERVs) are widespread viruses in vertebrate genome. ERVs arise when exogenous retrovirus infects germinal cells and spread in the genome of their hosts, transmitting its genetic material throughout the generations by means of Mendelian inheritance. ERVs are fundamental for the evolution of genomes, being responsible for some part of the genetic diversity of their hosts. The knowledge on ERVs in felids (Mammalia, Carnivora, Felidae) was basically restricted to domestic cats, and the diversity and patterns of evolution of these retroviral elements in other species were not known. This study aimed to investigate diversity, distribution and evolutionary patterns of ERVs in wildcat species. Hence, by utilizing molecular biology and bioinformatics tools, 85 endogenous retrovirus-like sequences were identified and characterized in eight representative Brazilian species: Leopardus pardalis, L. wiedii, L. colocolo, L. geoffroyi, L. tigrinus, Puma concolor, P. yagouaroundi and Panthera onca. The analyses of these novel felid ERVs showed the predominance of Gammaretroviruslike sequences, which is a characteristic pattern present in many mammal species. Phylogenetic analyses have evidenced three major groups of Gammaretrovirus, each one evolving in a peculiar manner. ERVs from different hosts were distributed in a mixed way in the phylogenies, differently of a coevolutionary pattern. However, more detailed analyses of some sequences demonstrated peculiarities, as in the case of a group of sequences similar to an ERV from the bat Myotis lucifugus. Notably, through phylogenetic analyses, and in comparison to data obtained in the literature, it may be suggested that some infection by a retrovirus occurred in a felid ancestral species in the second half of the Miocene. Therefore, the results obtained demonstrate that ERVs from Neotropical felids follow patterns which are very similar to the ones described for other mammals, also suggesting some cases of similar retrovirus lineage infecting different mammal orders.

Retrovírus endógenos (ERVs) são vírus altamente difundidos no genoma de vertebrados. ERVs surgem quando retrovírus exógenos infectam células germinativas e se disseminam no genoma de seus hospedeiros, transmitindo seu material genético através das gerações por meio de herança mendeliana. ERVs são fundamentais na evolução dos genomas, sendo eles responsáveis por uma parte da diversidade genética de seus hospedeiros. O conhecimento sobre ERVs na família Felidae (Mammalia, Carnivora) estava praticamente restrito ao gato doméstico, e não se conhecia diversidade e padrões de evolução desses retroelementos em outras espécies. Este estudo teve como objetivo investigar diversidade, distribuição e padrões evolutivos de ERVs em espécies de gatos silvestres. Utilizando ferramentas de biologia molecular e bioinformática, foram identificadas e caracterizadas 85 sequências similares a retrovírus endógenos nos representantes das oito espécies brasileiras: Leopardus pardalis, L. wiedii, L. colocolo, L. geoffroyi, L. tigrinus, Puma concolor, P. yagouaroundi e Panthera onca. Encontrou-se uma predominância de ERVs similares a Gammaretrovirus, um padrão característico em muitas espécies de mamíferos. As análises filogenéticas evidenciaram três grupos principais de Gammaretrovirus, cada um evoluindo de maneira peculiar. Em uma visão geral, os ERVs provenientes de diferentes hospedeiros apresentaram-se distribuídos de forma heterogênea nas filogenias, dificultando a constatação de um padrão coevolutivo. No entanto, análises mais detalhadas de algumas sequências demonstraram peculiaridades, como no caso de um grupo de sequências similares a de um ERV oriundo do morcego Myotis lucifugus. Através de análises filogenéticas em comparação com dados obtidos na literatura, sugere-se que a infecção desse retrovírus ocorreu em uma espécie ancestral de felídeo, na segunda metade do Mioceno. Os resultados obtidos permitiram demonstrar que os felídeos neotropicais apresentam ERVs que seguem padrões semelhantes aos descritos a respeito de outros mamíferos, sugerindo também alguns casos de infecções de retrovírus muito similares entre diferentes ordens de mamíferos. / Endogenous retroviruses (ERVs) are widespread viruses in vertebrate genome. ERVs arise when exogenous retrovirus infects germinal cells and spread in the genome of their hosts, transmitting its genetic material throughout the generations by means of Mendelian inheritance. ERVs are fundamental for the evolution of genomes, being responsible for some part of the genetic diversity of their hosts. The knowledge on ERVs in felids (Mammalia, Carnivora, Felidae) was basically restricted to domestic cats, and the diversity and patterns of evolution of these retroviral elements in other species were not known. This study aimed to investigate diversity, distribution and evolutionary patterns of ERVs in wildcat species. Hence, by utilizing molecular biology and bioinformatics tools, 85 endogenous retrovirus-like sequences were identified and characterized in eight representative Brazilian species: Leopardus pardalis, L. wiedii, L. colocolo, L. geoffroyi, L. tigrinus, Puma concolor, P. yagouaroundi and Panthera onca. The analyses of these novel felid ERVs showed the predominance of Gammaretroviruslike sequences, which is a characteristic pattern present in many mammal species. Phylogenetic analyses have evidenced three major groups of Gammaretrovirus, each one evolving in a peculiar manner. ERVs from different hosts were distributed in a mixed way in the phylogenies, differently of a coevolutionary pattern. However, more detailed analyses of some sequences demonstrated peculiarities, as in the case of a group of sequences similar to an ERV from the bat Myotis lucifugus. Notably, through phylogenetic analyses, and in comparison to data obtained in the literature, it may be suggested that some infection by a retrovirus occurred in a felid ancestral species in the second half of the Miocene. Therefore, the results obtained demonstrate that ERVs from Neotropical felids follow patterns which are very similar to the ones described for other mammals, also suggesting some cases of similar retrovirus lineage infecting different mammal orders.