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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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Unrooted tree of several LTRs (9<n<3) obtained in each of the following species of Malagasy lemurs.MMU: Microcebus murinus, MRA: M. ravelobensis, MTA: M. tavaratra, MSA: M. sambiranensis, MMY: M. myoxinus, MGR: M. griseorufus, CME: Cheirogaleus medius. See Table S4 for the voucher specimen numbers of the lemur samples used in this study. Numbers associated to internal branched correspond to Bayesian posterior probabilities ≥0.95/bootstrap ML values ≥80. The alignment used for the analyses is provided in Dataset S3.
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pgen-1000425-g006: Unrooted tree of several LTRs (9<n<3) obtained in each of the following species of Malagasy lemurs.MMU: Microcebus murinus, MRA: M. ravelobensis, MTA: M. tavaratra, MSA: M. sambiranensis, MMY: M. myoxinus, MGR: M. griseorufus, CME: Cheirogaleus medius. See Table S4 for the voucher specimen numbers of the lemur samples used in this study. Numbers associated to internal branched correspond to Bayesian posterior probabilities ≥0.95/bootstrap ML values ≥80. The alignment used for the analyses is provided in Dataset S3.

Mentions: Also consistent with the hypothesis of two independent germline infiltrations, the Southern blot (Figure 2) and PCR screening (Figure 5) of pSIV insertions in six Microcebus species and Cheirogaleus did not reveal any shared orthologous insertion between Microcebus and Cheirogaleus, as would be expected under the single ancestral germline infiltration model. In addition, sequencing and phylogenetic analysis of multiple pSIV LTRs from the different species of Microcebus and from C. medius yielded two distinct monophyletic clades that correspond to the two lemur genera (Figure 6). This shows that pSIVfdl and pSIVgml most likely derive from two closely related but distinct circulating lentiviruses, although the possibility of a gene conversion effect that would have homogenized the different LTRs in both species cannot be excluded [25].


Parallel germline infiltration of a lentivirus in two Malagasy lemurs.

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

Unrooted tree of several LTRs (9<n<3) obtained in each of the following species of Malagasy lemurs.MMU: Microcebus murinus, MRA: M. ravelobensis, MTA: M. tavaratra, MSA: M. sambiranensis, MMY: M. myoxinus, MGR: M. griseorufus, CME: Cheirogaleus medius. See Table S4 for the voucher specimen numbers of the lemur samples used in this study. Numbers associated to internal branched correspond to Bayesian posterior probabilities ≥0.95/bootstrap ML values ≥80. The alignment used for the analyses is provided in Dataset S3.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1000425-g006: Unrooted tree of several LTRs (9<n<3) obtained in each of the following species of Malagasy lemurs.MMU: Microcebus murinus, MRA: M. ravelobensis, MTA: M. tavaratra, MSA: M. sambiranensis, MMY: M. myoxinus, MGR: M. griseorufus, CME: Cheirogaleus medius. See Table S4 for the voucher specimen numbers of the lemur samples used in this study. Numbers associated to internal branched correspond to Bayesian posterior probabilities ≥0.95/bootstrap ML values ≥80. The alignment used for the analyses is provided in Dataset S3.
Mentions: Also consistent with the hypothesis of two independent germline infiltrations, the Southern blot (Figure 2) and PCR screening (Figure 5) of pSIV insertions in six Microcebus species and Cheirogaleus did not reveal any shared orthologous insertion between Microcebus and Cheirogaleus, as would be expected under the single ancestral germline infiltration model. In addition, sequencing and phylogenetic analysis of multiple pSIV LTRs from the different species of Microcebus and from C. medius yielded two distinct monophyletic clades that correspond to the two lemur genera (Figure 6). This shows that pSIVfdl and pSIVgml most likely derive from two closely related but distinct circulating lentiviruses, although the possibility of a gene conversion effect that would have homogenized the different LTRs in both species cannot be excluded [25].

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