Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma

ABSTRACT Kaposi’s sarcoma (KS), caused by KS-associated herpesvirus (KSHV), is the most common cancer among HIV-infected patients in Malawi and in the United States today. In Malawi, KSHV is endemic. We conducted a cross-sectional study of patients with HIV infection and KS with no history of chemo-...

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Autores principales:	Mina C. Hosseinipour, Kristen M. Sweet, Jie Xiong, Dan Namarika, Albert Mwafongo, Michael Nyirenda, Loreen Chiwoko, Deborah Kamwendo, Irving Hoffman, Jeannette Lee, Sam Phiri, Wolfgang Vahrson, Blossom Damania, Dirk P. Dittmer
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e2552bd5127547a58badd56978889fa5
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spelling	oai:doaj.org-article:e2552bd5127547a58badd56978889fa52021-11-15T15:45:54ZViral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma10.1128/mBio.01633-142150-7511https://doaj.org/article/e2552bd5127547a58badd56978889fa52014-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01633-14https://doaj.org/toc/2150-7511ABSTRACT Kaposi’s sarcoma (KS), caused by KS-associated herpesvirus (KSHV), is the most common cancer among HIV-infected patients in Malawi and in the United States today. In Malawi, KSHV is endemic. We conducted a cross-sectional study of patients with HIV infection and KS with no history of chemo- or antiretroviral therapy (ART). Seventy patients were enrolled. Eighty-one percent had T1 (advanced) KS. Median CD4 and HIV RNA levels were 181 cells/mm3 and 138,641 copies/ml, respectively. We had complete information and suitable plasma and biopsy samples for 66 patients. For 59/66 (89%) patients, a detectable KSHV load was found in plasma (median, 2,291 copies/ml; interquartile range [IQR], 741 to 5,623). We utilized a novel KSHV real-time quantitative PCR (qPCR) array with multiple primers per open reading frame to examine KSHV transcription. Seventeen samples exhibited only minimal levels of KSHV mRNAs, presumably due to the limited number of infected cells. For all other biopsy samples, the viral latency locus (LANA, vCyc, vFLIP, kaposin, and microRNAs [miRNAs]) was transcribed abundantly, as was K15 mRNA. We could identify two subtypes of treatment-naive KS: lesions that transcribed viral RNAs across the length of the viral genome and lesions that displayed only limited transcription restricted to the latency locus. This finding demonstrates for the first time the existence of multiple subtypes of KS lesions in HIV- and KS-treatment naive patients. IMPORTANCE KS is the leading cancer in people infected with HIV worldwide and is causally linked to KSHV infection. Using viral transcription profiling, we have demonstrated the existence of multiple subtypes of KS lesions for the first time in HIV- and KS-treatment-naive patients. A substantial number of lesions transcribe mRNAs which encode the viral kinases and hence could be targeted by the antiviral drugs ganciclovir or AZT in addition to chemotherapy.Mina C. HosseinipourKristen M. SweetJie XiongDan NamarikaAlbert MwafongoMichael NyirendaLoreen ChiwokoDeborah KamwendoIrving HoffmanJeannette LeeSam PhiriWolfgang VahrsonBlossom DamaniaDirk P. DittmerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 5 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Mina C. Hosseinipour Kristen M. Sweet Jie Xiong Dan Namarika Albert Mwafongo Michael Nyirenda Loreen Chiwoko Deborah Kamwendo Irving Hoffman Jeannette Lee Sam Phiri Wolfgang Vahrson Blossom Damania Dirk P. Dittmer Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma
description	ABSTRACT Kaposi’s sarcoma (KS), caused by KS-associated herpesvirus (KSHV), is the most common cancer among HIV-infected patients in Malawi and in the United States today. In Malawi, KSHV is endemic. We conducted a cross-sectional study of patients with HIV infection and KS with no history of chemo- or antiretroviral therapy (ART). Seventy patients were enrolled. Eighty-one percent had T1 (advanced) KS. Median CD4 and HIV RNA levels were 181 cells/mm3 and 138,641 copies/ml, respectively. We had complete information and suitable plasma and biopsy samples for 66 patients. For 59/66 (89%) patients, a detectable KSHV load was found in plasma (median, 2,291 copies/ml; interquartile range [IQR], 741 to 5,623). We utilized a novel KSHV real-time quantitative PCR (qPCR) array with multiple primers per open reading frame to examine KSHV transcription. Seventeen samples exhibited only minimal levels of KSHV mRNAs, presumably due to the limited number of infected cells. For all other biopsy samples, the viral latency locus (LANA, vCyc, vFLIP, kaposin, and microRNAs [miRNAs]) was transcribed abundantly, as was K15 mRNA. We could identify two subtypes of treatment-naive KS: lesions that transcribed viral RNAs across the length of the viral genome and lesions that displayed only limited transcription restricted to the latency locus. This finding demonstrates for the first time the existence of multiple subtypes of KS lesions in HIV- and KS-treatment naive patients. IMPORTANCE KS is the leading cancer in people infected with HIV worldwide and is causally linked to KSHV infection. Using viral transcription profiling, we have demonstrated the existence of multiple subtypes of KS lesions for the first time in HIV- and KS-treatment-naive patients. A substantial number of lesions transcribe mRNAs which encode the viral kinases and hence could be targeted by the antiviral drugs ganciclovir or AZT in addition to chemotherapy.
format	article
author	Mina C. Hosseinipour Kristen M. Sweet Jie Xiong Dan Namarika Albert Mwafongo Michael Nyirenda Loreen Chiwoko Deborah Kamwendo Irving Hoffman Jeannette Lee Sam Phiri Wolfgang Vahrson Blossom Damania Dirk P. Dittmer
author_facet	Mina C. Hosseinipour Kristen M. Sweet Jie Xiong Dan Namarika Albert Mwafongo Michael Nyirenda Loreen Chiwoko Deborah Kamwendo Irving Hoffman Jeannette Lee Sam Phiri Wolfgang Vahrson Blossom Damania Dirk P. Dittmer
author_sort	Mina C. Hosseinipour
title	Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma
title_short	Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma
title_full	Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma
title_fullStr	Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma
title_full_unstemmed	Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma
title_sort	viral profiling identifies multiple subtypes of kaposi’s sarcoma
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/e2552bd5127547a58badd56978889fa5
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Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma

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