dc.contributor.author |
Rangel Lopes de Campos, W
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dc.contributor.author |
Chirwa, N
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dc.contributor.author |
London, G
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dc.contributor.author |
Rotherham, LS
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dc.contributor.author |
Morris, L
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dc.contributor.author |
Mayosi, BM
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dc.contributor.author |
Khati, M
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dc.date.accessioned |
2015-08-19T10:49:57Z |
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dc.date.available |
2015-08-19T10:49:57Z |
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dc.date.issued |
2014-10 |
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dc.identifier.citation |
Lopes de Campos, W, Chirwa, N, London, G, Rotherham, LS, Morris, L, Mayosi, BM, and Khati, M. 2014. H HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-Gp120 aptamer. PLOS One Journal, vol. 9(10), pp 1-9 |
en_US |
dc.identifier.issn |
1932-6203 |
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dc.identifier.uri |
http://hdl.handle.net/10204/8057
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|
dc.description |
Copyright: Public Library of Science 2014. |
en_US |
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_US |
dc.language.iso |
en |
en_US |
dc.publisher |
Public Library of Science |
en_US |
dc.relation.ispartofseries |
Workflow;14641 |
|
dc.subject |
HIV-associated cardiomyopathy |
en_US |
dc.subject |
HIVCM |
en_US |
dc.subject |
HIV-1 subtype C infection |
en_US |
dc.subject |
Human cardiomyocytes |
en_US |
dc.title |
HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-Gp120 aptamer |
en_US |
dc.type |
Article |
en_US |
dc.identifier.apacitation |
Rangel Lopes de Campos, W., Chirwa, N., London, G., Rotherham, L., Morris, L., Mayosi, B., & Khati, M. (2014). HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-Gp120 aptamer. http://hdl.handle.net/10204/8057 |
en_ZA |
dc.identifier.chicagocitation |
Rangel Lopes de Campos, W, N Chirwa, G London, LS Rotherham, L Morris, BM Mayosi, and M Khati "HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-Gp120 aptamer." (2014) http://hdl.handle.net/10204/8057 |
en_ZA |
dc.identifier.vancouvercitation |
Rangel Lopes de Campos W, Chirwa N, London G, Rotherham L, Morris L, Mayosi B, et al. HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-Gp120 aptamer. 2014; http://hdl.handle.net/10204/8057. |
en_ZA |
dc.identifier.ris |
TY - Article
AU - Rangel Lopes de Campos, W
AU - Chirwa, N
AU - London, G
AU - Rotherham, LS
AU - Morris, L
AU - Mayosi, BM
AU - Khati, M
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 - 2014-10
DB - ResearchSpace
DP - CSIR
KW - HIV-associated cardiomyopathy
KW - HIVCM
KW - HIV-1 subtype C infection
KW - Human cardiomyocytes
LK - https://researchspace.csir.co.za
PY - 2014
SM - 1932-6203
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/10204/8057
ER -
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en_ZA |