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Genetic diversity of koala retroviral envelopes.

Xu W, Gorman K, Santiago JC, Kluska K, Eiden MV - Viruses (2015)

Bottom Line: Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies.More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas.We have now obtained a number of additional KoRV envelope variants.

View Article: PubMed Central - PubMed

Affiliation: Section on Directed Gene Transfer, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. xuwenqin@mail.nih.gov.

ABSTRACT
Genetic diversity, attributable to the low fidelity of reverse transcription, recombination and mutation, is an important feature of infectious retroviruses. Under selective pressure, such as that imposed by superinfection interference, gammaretroviruses commonly adapt their envelope proteins to use alternative receptors to overcome this entry block. The first characterized koala retroviruses KoRV subgroup A (KoRV-A) were remarkable in their absence of envelope genetic variability. Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies. More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas. The envelope proteins of KoRV-A and KoRV-B are sufficiently divergent to confer the ability to bind and employ distinct receptors for infection. We have now obtained a number of additional KoRV envelope variants. In the present studies we report these variants, and show that they differ from KoRV-A and KoRV-B envelopes in their host range and superinfection interference properties. Thus, there appears to be considerable variation among KoRVs envelope genes suggesting genetic diversity is a factor following the KoRV-A infection process.

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Mechanism of KoRV enveloped retroviral transmission in koalas infected with KoRV-A (represented as koalas within blue circles), KoRV-B (red encircled koalas) and/or KoRV-F (koalas within purple circles). The small circles represent KoRV viral particles composed of KoRV-A, B, or F envelopes (blue, red or purple, respectively) and the folded lines within the circles represent the KoRV-A, KoRV-B or KoRV-F genomes (red, blue or purple lines, respectively). KoRV-A positive animals are resistant to superinfection by KoRV-A (top most figure) but the KoRV-A genome (blue) can be transmitted in particles bearing KoRV-B (red) or KoRV-F (purple) envelopes.
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viruses-07-01258-f006: Mechanism of KoRV enveloped retroviral transmission in koalas infected with KoRV-A (represented as koalas within blue circles), KoRV-B (red encircled koalas) and/or KoRV-F (koalas within purple circles). The small circles represent KoRV viral particles composed of KoRV-A, B, or F envelopes (blue, red or purple, respectively) and the folded lines within the circles represent the KoRV-A, KoRV-B or KoRV-F genomes (red, blue or purple lines, respectively). KoRV-A positive animals are resistant to superinfection by KoRV-A (top most figure) but the KoRV-A genome (blue) can be transmitted in particles bearing KoRV-B (red) or KoRV-F (purple) envelopes.

Mentions: KoRV-A is a newly endogenized retrovirus that has been resident in the koala genome for several decades to a maximum age of approximately 22,200–49,900 years ago [9,25]. To date, there exists no evidence of KoRV-A horizontal transmission as an infectious virus [9]. KoRV-B and KoRV-F have only been isolated from koalas infected with KoRV-A [14,15]. Thus KoRV-B and KoRV-F may provide a means of mobilizing endogenous KoRV-A by circumventing the superinfection interference block present in koala in which KoRV-A exists as an endogenous virus. Indeed it has been demonstrated that KoRV transcript levels in plasma are significantly increased in animals suffering from neoplasias such as lymphoma when compared to KoRV-A positive healthy animals [26]. Taking into account that the primers used in these studies amplify a region of the polymerase gene conserved between KoRV-A and other KoRV variants the observed increased viral RNA levels could be attributable to KoRV-B or KoRV-F (Figure 6). The genome of KoRV-F has not been sequenced in its entirety, therefore, it is presently unknown whether KoRV-F represents a defective or full length replication competent genome.


Genetic diversity of koala retroviral envelopes.

Xu W, Gorman K, Santiago JC, Kluska K, Eiden MV - Viruses (2015)

Mechanism of KoRV enveloped retroviral transmission in koalas infected with KoRV-A (represented as koalas within blue circles), KoRV-B (red encircled koalas) and/or KoRV-F (koalas within purple circles). The small circles represent KoRV viral particles composed of KoRV-A, B, or F envelopes (blue, red or purple, respectively) and the folded lines within the circles represent the KoRV-A, KoRV-B or KoRV-F genomes (red, blue or purple lines, respectively). KoRV-A positive animals are resistant to superinfection by KoRV-A (top most figure) but the KoRV-A genome (blue) can be transmitted in particles bearing KoRV-B (red) or KoRV-F (purple) envelopes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4379569&req=5

viruses-07-01258-f006: Mechanism of KoRV enveloped retroviral transmission in koalas infected with KoRV-A (represented as koalas within blue circles), KoRV-B (red encircled koalas) and/or KoRV-F (koalas within purple circles). The small circles represent KoRV viral particles composed of KoRV-A, B, or F envelopes (blue, red or purple, respectively) and the folded lines within the circles represent the KoRV-A, KoRV-B or KoRV-F genomes (red, blue or purple lines, respectively). KoRV-A positive animals are resistant to superinfection by KoRV-A (top most figure) but the KoRV-A genome (blue) can be transmitted in particles bearing KoRV-B (red) or KoRV-F (purple) envelopes.
Mentions: KoRV-A is a newly endogenized retrovirus that has been resident in the koala genome for several decades to a maximum age of approximately 22,200–49,900 years ago [9,25]. To date, there exists no evidence of KoRV-A horizontal transmission as an infectious virus [9]. KoRV-B and KoRV-F have only been isolated from koalas infected with KoRV-A [14,15]. Thus KoRV-B and KoRV-F may provide a means of mobilizing endogenous KoRV-A by circumventing the superinfection interference block present in koala in which KoRV-A exists as an endogenous virus. Indeed it has been demonstrated that KoRV transcript levels in plasma are significantly increased in animals suffering from neoplasias such as lymphoma when compared to KoRV-A positive healthy animals [26]. Taking into account that the primers used in these studies amplify a region of the polymerase gene conserved between KoRV-A and other KoRV variants the observed increased viral RNA levels could be attributable to KoRV-B or KoRV-F (Figure 6). The genome of KoRV-F has not been sequenced in its entirety, therefore, it is presently unknown whether KoRV-F represents a defective or full length replication competent genome.

Bottom Line: Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies.More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas.We have now obtained a number of additional KoRV envelope variants.

View Article: PubMed Central - PubMed

Affiliation: Section on Directed Gene Transfer, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. xuwenqin@mail.nih.gov.

ABSTRACT
Genetic diversity, attributable to the low fidelity of reverse transcription, recombination and mutation, is an important feature of infectious retroviruses. Under selective pressure, such as that imposed by superinfection interference, gammaretroviruses commonly adapt their envelope proteins to use alternative receptors to overcome this entry block. The first characterized koala retroviruses KoRV subgroup A (KoRV-A) were remarkable in their absence of envelope genetic variability. Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies. More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas. The envelope proteins of KoRV-A and KoRV-B are sufficiently divergent to confer the ability to bind and employ distinct receptors for infection. We have now obtained a number of additional KoRV envelope variants. In the present studies we report these variants, and show that they differ from KoRV-A and KoRV-B envelopes in their host range and superinfection interference properties. Thus, there appears to be considerable variation among KoRVs envelope genes suggesting genetic diversity is a factor following the KoRV-A infection process.

Show MeSH
Related in: MedlinePlus