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Koala retrovirus diversity, transmissibility, and disease associations

BACKGROUND: Koalas are infected with the koala retrovirus (KoRV) that exists as exogenous or endogenous viruses. KoRV is genetically diverse with co-infection with up to ten envelope subtypes (A-J) possible; KoRV-A is the prototype endogenous form. KoRV-B, first found in a small number of koalas wit...

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Autores principales: Zheng, HaoQiang, Pan, Yi, Tang, Shaohua, Pye, Geoffrey W., Stadler, Cynthia K., Vogelnest, Larry, Herrin, Kimberly Vinette, Rideout, Bruce A., Switzer, William M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530975/
https://www.ncbi.nlm.nih.gov/pubmed/33008414
http://dx.doi.org/10.1186/s12977-020-00541-1
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author Zheng, HaoQiang
Pan, Yi
Tang, Shaohua
Pye, Geoffrey W.
Stadler, Cynthia K.
Vogelnest, Larry
Herrin, Kimberly Vinette
Rideout, Bruce A.
Switzer, William M.
author_facet Zheng, HaoQiang
Pan, Yi
Tang, Shaohua
Pye, Geoffrey W.
Stadler, Cynthia K.
Vogelnest, Larry
Herrin, Kimberly Vinette
Rideout, Bruce A.
Switzer, William M.
author_sort Zheng, HaoQiang
collection PubMed
description BACKGROUND: Koalas are infected with the koala retrovirus (KoRV) that exists as exogenous or endogenous viruses. KoRV is genetically diverse with co-infection with up to ten envelope subtypes (A-J) possible; KoRV-A is the prototype endogenous form. KoRV-B, first found in a small number of koalas with an increased leukemia prevalence at one US zoo, has been associated with other cancers and increased chlamydial disease. To better understand the molecular epidemiology of KoRV variants and the effect of increased viral loads (VLs) on transmissibility and pathogenicity we developed subtype-specific quantitative PCR (qPCR) assays and tested blood and tissue samples from koalas at US zoos (n = 78), two Australian zoos (n = 27) and wild-caught (n = 21) in Australia. We analyzed PCR results with available clinical, demographic, and pedigree data. RESULTS: All koalas were KoRV-A-infected. A small number of koalas (10.3%) at one US zoo were also infected with non-A subtypes, while a higher non-A subtype prevalence (59.3%) was found in koalas at Australian zoos. Wild koalas from one location were only infected with KoRV-A. We observed a significant association of infection and plasma VLs of non-A subtypes in koalas that died of leukemia/lymphoma and other neoplasias and report cancer diagnoses in KoRV-A-positive animals. Infection and VLs of non-A subtypes was not associated with age or sex. Transmission of non-A subtypes occurred from dam-to-offspring and likely following adult-to-adult contact, but associations with contact type were not evaluated. Brief antiretroviral treatment of one leukemic koala infected with high plasma levels of KoRV-A, -B, and -F did not affect VL or disease progression. CONCLUSIONS: Our results show a significant association of non-A KoRV infection and plasma VLs with leukemia and other cancers. Although we confirm dam-to-offspring transmission of these variants, we also show other routes are possible. Our validated qPCR assays will be useful to further understand KoRV epidemiology and its zoonotic transmission potential for humans exposed to koalas because KoRV can infect human cells.
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spelling pubmed-75309752020-10-05 Koala retrovirus diversity, transmissibility, and disease associations Zheng, HaoQiang Pan, Yi Tang, Shaohua Pye, Geoffrey W. Stadler, Cynthia K. Vogelnest, Larry Herrin, Kimberly Vinette Rideout, Bruce A. Switzer, William M. Retrovirology Research BACKGROUND: Koalas are infected with the koala retrovirus (KoRV) that exists as exogenous or endogenous viruses. KoRV is genetically diverse with co-infection with up to ten envelope subtypes (A-J) possible; KoRV-A is the prototype endogenous form. KoRV-B, first found in a small number of koalas with an increased leukemia prevalence at one US zoo, has been associated with other cancers and increased chlamydial disease. To better understand the molecular epidemiology of KoRV variants and the effect of increased viral loads (VLs) on transmissibility and pathogenicity we developed subtype-specific quantitative PCR (qPCR) assays and tested blood and tissue samples from koalas at US zoos (n = 78), two Australian zoos (n = 27) and wild-caught (n = 21) in Australia. We analyzed PCR results with available clinical, demographic, and pedigree data. RESULTS: All koalas were KoRV-A-infected. A small number of koalas (10.3%) at one US zoo were also infected with non-A subtypes, while a higher non-A subtype prevalence (59.3%) was found in koalas at Australian zoos. Wild koalas from one location were only infected with KoRV-A. We observed a significant association of infection and plasma VLs of non-A subtypes in koalas that died of leukemia/lymphoma and other neoplasias and report cancer diagnoses in KoRV-A-positive animals. Infection and VLs of non-A subtypes was not associated with age or sex. Transmission of non-A subtypes occurred from dam-to-offspring and likely following adult-to-adult contact, but associations with contact type were not evaluated. Brief antiretroviral treatment of one leukemic koala infected with high plasma levels of KoRV-A, -B, and -F did not affect VL or disease progression. CONCLUSIONS: Our results show a significant association of non-A KoRV infection and plasma VLs with leukemia and other cancers. Although we confirm dam-to-offspring transmission of these variants, we also show other routes are possible. Our validated qPCR assays will be useful to further understand KoRV epidemiology and its zoonotic transmission potential for humans exposed to koalas because KoRV can infect human cells. BioMed Central 2020-10-02 /pmc/articles/PMC7530975/ /pubmed/33008414 http://dx.doi.org/10.1186/s12977-020-00541-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zheng, HaoQiang
Pan, Yi
Tang, Shaohua
Pye, Geoffrey W.
Stadler, Cynthia K.
Vogelnest, Larry
Herrin, Kimberly Vinette
Rideout, Bruce A.
Switzer, William M.
Koala retrovirus diversity, transmissibility, and disease associations
title Koala retrovirus diversity, transmissibility, and disease associations
title_full Koala retrovirus diversity, transmissibility, and disease associations
title_fullStr Koala retrovirus diversity, transmissibility, and disease associations
title_full_unstemmed Koala retrovirus diversity, transmissibility, and disease associations
title_short Koala retrovirus diversity, transmissibility, and disease associations
title_sort koala retrovirus diversity, transmissibility, and disease associations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530975/
https://www.ncbi.nlm.nih.gov/pubmed/33008414
http://dx.doi.org/10.1186/s12977-020-00541-1
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