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Parallel germline infiltration of a lentivirus in two Malagasy lemurs.

Gilbert C, Maxfield DG, Goodman SM, Feschotte C - PLoS Genet. (2009)

Bottom Line: Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration.Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago.These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Texas at Arlington, Arlington, TX, USA.

ABSTRACT
Retroviruses normally infect the somatic cells of their host and are transmitted horizontally, i.e., in an exogenous way. Occasionally, however, some retroviruses can also infect and integrate into the genome of germ cells, which may allow for their vertical inheritance and fixation in a given species; a process known as endogenization. Lentiviruses, a group of mammalian retroviruses that includes HIV, are known to infect primates, ruminants, horses, and cats. Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration. Here, we report on the discovery of endogenous lentiviral insertions in seven species of Malagasy lemurs from two different genera -- Cheirogaleus and Microcebus. Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago. In addition, we demonstrate that this lentivirus independently infiltrated the germline of Cheirogaleus and that the two endogenization events occurred quasi-simultaneously. Using multiple proviral copies, we derive and characterize an apparently full length and intact consensus for this lentivirus. These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses. The study sets the stage for an unprecedented opportunity to reconstruct an ancestral primate lentivirus and thereby advance our knowledge of host-virus interactions.

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Related in: MedlinePlus

Unrooted tree of lentiviruses obtained after phylogenetic analysis of an alignment including ∼2350 nucleotides of the gag-pol region.Numbers associated to internal branches correspond to Bayesian posterior probabilities/bootstrap ML values. Asterisks indicate when an internal branch is supported by posterior probability = 1/bootstrap = 100. Accession numbers of the sequences are listed in Table S2. The alignment used for the analyses is provided in Dataset S2.
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pgen-1000425-g004: Unrooted tree of lentiviruses obtained after phylogenetic analysis of an alignment including ∼2350 nucleotides of the gag-pol region.Numbers associated to internal branches correspond to Bayesian posterior probabilities/bootstrap ML values. Asterisks indicate when an internal branch is supported by posterior probability = 1/bootstrap = 100. Accession numbers of the sequences are listed in Table S2. The alignment used for the analyses is provided in Dataset S2.

Mentions: In order to formally assess the phylogenetic relationships between pSIV and other retroviruses, we performed Bayesian and Maximum Likelihood (ML) phylogenetic analyses of the well-conserved reverse transcriptase (RT) domain. Both methods unequivocally support the grouping of pSIV within the lentivirus clade (Figure S5). Furthermore, as the RT alone does not provide any phylogenetic resolution between the different genera of lentiviruses, we also conducted Bayesian and ML analyses of the pol and gag domains extracted from a diverse set of lentiviruses. Separate analysis of the two domains did not reveal any obvious recombination event, i.e., the gag tree was not incongruent with the pol tree (not shown). In agreement with Gifford et al. [12], the Bayesian analysis combining gag and pol provided strong support for a potential sister relationship between pSIV and other primate lentiviruses, but this grouping is somewhat equivocal since the support was much lower in the ML analysis (Figure 4). Regardless, we believe that pSIV is sufficiently distant from the other known lentiviruses to be considered as a distinct lentiviral species.


Parallel germline infiltration of a lentivirus in two Malagasy lemurs.

Gilbert C, Maxfield DG, Goodman SM, Feschotte C - PLoS Genet. (2009)

Unrooted tree of lentiviruses obtained after phylogenetic analysis of an alignment including ∼2350 nucleotides of the gag-pol region.Numbers associated to internal branches correspond to Bayesian posterior probabilities/bootstrap ML values. Asterisks indicate when an internal branch is supported by posterior probability = 1/bootstrap = 100. Accession numbers of the sequences are listed in Table S2. The alignment used for the analyses is provided in Dataset S2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651035&req=5

pgen-1000425-g004: Unrooted tree of lentiviruses obtained after phylogenetic analysis of an alignment including ∼2350 nucleotides of the gag-pol region.Numbers associated to internal branches correspond to Bayesian posterior probabilities/bootstrap ML values. Asterisks indicate when an internal branch is supported by posterior probability = 1/bootstrap = 100. Accession numbers of the sequences are listed in Table S2. The alignment used for the analyses is provided in Dataset S2.
Mentions: In order to formally assess the phylogenetic relationships between pSIV and other retroviruses, we performed Bayesian and Maximum Likelihood (ML) phylogenetic analyses of the well-conserved reverse transcriptase (RT) domain. Both methods unequivocally support the grouping of pSIV within the lentivirus clade (Figure S5). Furthermore, as the RT alone does not provide any phylogenetic resolution between the different genera of lentiviruses, we also conducted Bayesian and ML analyses of the pol and gag domains extracted from a diverse set of lentiviruses. Separate analysis of the two domains did not reveal any obvious recombination event, i.e., the gag tree was not incongruent with the pol tree (not shown). In agreement with Gifford et al. [12], the Bayesian analysis combining gag and pol provided strong support for a potential sister relationship between pSIV and other primate lentiviruses, but this grouping is somewhat equivocal since the support was much lower in the ML analysis (Figure 4). Regardless, we believe that pSIV is sufficiently distant from the other known lentiviruses to be considered as a distinct lentiviral species.

Bottom Line: Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration.Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago.These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Texas at Arlington, Arlington, TX, USA.

ABSTRACT
Retroviruses normally infect the somatic cells of their host and are transmitted horizontally, i.e., in an exogenous way. Occasionally, however, some retroviruses can also infect and integrate into the genome of germ cells, which may allow for their vertical inheritance and fixation in a given species; a process known as endogenization. Lentiviruses, a group of mammalian retroviruses that includes HIV, are known to infect primates, ruminants, horses, and cats. Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration. Here, we report on the discovery of endogenous lentiviral insertions in seven species of Malagasy lemurs from two different genera -- Cheirogaleus and Microcebus. Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago. In addition, we demonstrate that this lentivirus independently infiltrated the germline of Cheirogaleus and that the two endogenization events occurred quasi-simultaneously. Using multiple proviral copies, we derive and characterize an apparently full length and intact consensus for this lentivirus. These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses. The study sets the stage for an unprecedented opportunity to reconstruct an ancestral primate lentivirus and thereby advance our knowledge of host-virus interactions.

Show MeSH
Related in: MedlinePlus