HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-gp120 aptamer

 

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dc.contributor.author de Campos, Walter R Lopes en_ZA
dc.contributor.author Chirwa, Nthato en_ZA
dc.contributor.author London, Grace en_ZA
dc.contributor.author Rotherham, Lia S en_ZA
dc.contributor.author Morris, Lynn en_ZA
dc.contributor.author Mayosi, Bongani M en_ZA
dc.contributor.author Khati, Makobetsa en_ZA
dc.date.accessioned 2015-11-23T12:37:03Z
dc.date.available 2015-11-23T12:37:03Z
dc.date.issued 2014 en_ZA
dc.identifier.citation de Campos, W. R. L., Chirwa, N., London, G., Rotherham, L. S., Morris, L., Mayosi, B. M., & Khati, M. (2014). HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-gp120 aptamer. PloS one, 9(10), e110930-e110930. doi:10.1371/journal.pone.0110930 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15354
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0110930
dc.description.abstract HIV-associated cardiomyopathy (HIVCM) is of clinical concern in developing countries because of a high HIV-1 prevalence, especially subtype C, and limited access to highly active antiretroviral therapy (HAART). For these reasons, we investigated the direct and indirect effects of HIV-1 subtype C infection of cultured human cardiomyocytes and the mechanisms leading to cardiomyocytes damage; as well as a way to mitigate the damage. We evaluated a novel approach to mitigate HIVCM using a previously reported gp120 binding and HIV-1 neutralizing aptamer called UCLA1. We established a cell-based model of HIVCM by infecting human cardiomyocytes with cell-free HIV-1 or co-culturing human cardiomyocytes with HIV-infected monocyte derived macrophages (MDM). We discovered that HIV-1 subtype C unproductively (i.e. its life cycle is arrested after reverse transcription) infects cardiomyocytes. Furthermore, we found that HIV-1 initiates apoptosis of cardiomyocytes through caspase-9 activation, preferentially via the intrinsic or mitochondrial initiated pathway. CXCR4 receptor-using viruses were stronger inducers of apoptosis than CCR5 utilizing variants. Importantly, we discovered that HIV-1 induced apoptosis of cardiomyocytes was mitigated by UCLA1. However, UCLA1 had no protective effective on cardiomyocytes when apoptosis was triggered by HIV-infected MDM. When HIV-1 was treated with UCLA1 prior to infection of MDM, it failed to induce apoptosis of cardiomyocytes. These data suggest that HIV-1 causes a mitochondrial initiated apoptotic cascade, which signal through caspase-9, whereas HIV-1 infected MDM causes apoptosis predominantly via the death-receptor pathway, mediated by caspase-8. Furthermore the data suggest that UCLA1 protects cardiomyocytes from caspase-mediated apoptosis, directly by binding to HIV-1 and indirectly by preventing infection of MDM. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Apoptosis en_ZA
dc.subject.other HIV-1 en_ZA
dc.subject.other Macrophages en_ZA
dc.subject.other Cell staining en_ZA
dc.subject.other HIV en_ZA
dc.subject.other Coreceptors en_ZA
dc.subject.other Mitochondria en_ZA
dc.subject.other Monocytes en_ZA
dc.title HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-gp120 aptamer en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2014 Lopes de Campos et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Department of Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation de Campos, W. R. L., Chirwa, N., London, G., Rotherham, L. S., Morris, L., Mayosi, B. M., & Khati, M. (2014). HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-gp120 aptamer. <i>PLoS One</i>, http://hdl.handle.net/11427/15354 en_ZA
dc.identifier.chicagocitation de Campos, Walter R Lopes, Nthato Chirwa, Grace London, Lia S Rotherham, Lynn Morris, Bongani M Mayosi, and Makobetsa Khati "HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-gp120 aptamer." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/15354 en_ZA
dc.identifier.vancouvercitation de Campos WRL, Chirwa N, London G, Rotherham LS, Morris L, Mayosi BM, et al. HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-gp120 aptamer. PLoS One. 2014; http://hdl.handle.net/11427/15354. en_ZA
dc.identifier.ris TY - Journal Article AU - de Campos, Walter R Lopes AU - Chirwa, Nthato AU - London, Grace AU - Rotherham, Lia S AU - Morris, Lynn AU - Mayosi, Bongani M AU - Khati, Makobetsa AB - HIV-associated cardiomyopathy (HIVCM) is of clinical concern in developing countries because of a high HIV-1 prevalence, especially subtype C, and limited access to highly active antiretroviral therapy (HAART). For these reasons, we investigated the direct and indirect effects of HIV-1 subtype C infection of cultured human cardiomyocytes and the mechanisms leading to cardiomyocytes damage; as well as a way to mitigate the damage. We evaluated a novel approach to mitigate HIVCM using a previously reported gp120 binding and HIV-1 neutralizing aptamer called UCLA1. We established a cell-based model of HIVCM by infecting human cardiomyocytes with cell-free HIV-1 or co-culturing human cardiomyocytes with HIV-infected monocyte derived macrophages (MDM). We discovered that HIV-1 subtype C unproductively (i.e. its life cycle is arrested after reverse transcription) infects cardiomyocytes. Furthermore, we found that HIV-1 initiates apoptosis of cardiomyocytes through caspase-9 activation, preferentially via the intrinsic or mitochondrial initiated pathway. CXCR4 receptor-using viruses were stronger inducers of apoptosis than CCR5 utilizing variants. Importantly, we discovered that HIV-1 induced apoptosis of cardiomyocytes was mitigated by UCLA1. However, UCLA1 had no protective effective on cardiomyocytes when apoptosis was triggered by HIV-infected MDM. When HIV-1 was treated with UCLA1 prior to infection of MDM, it failed to induce apoptosis of cardiomyocytes. These data suggest that HIV-1 causes a mitochondrial initiated apoptotic cascade, which signal through caspase-9, whereas HIV-1 infected MDM causes apoptosis predominantly via the death-receptor pathway, mediated by caspase-8. Furthermore the data suggest that UCLA1 protects cardiomyocytes from caspase-mediated apoptosis, directly by binding to HIV-1 and indirectly by preventing infection of MDM. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0110930 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-gp120 aptamer TI - HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-gp120 aptamer UR - http://hdl.handle.net/11427/15354 ER - en_ZA


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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.