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-...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2014-10-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01633-14 |
| _version_ | 1818826611463553024 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T00:30:25Z |
| format | Article |
| id | doaj.art-e2552bd5127547a58badd56978889fa5 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T00:30:25Z |
| publishDate | 2014-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-e2552bd5127547a58badd56978889fa52022-12-21T20:45:06ZengAmerican Society for MicrobiologymBio2150-75112014-10-015510.1128/mBio.01633-14Viral Profiling Identifies Multiple Subtypes of Kaposi’s SarcomaMina C. Hosseinipour0Kristen M. Sweet1Jie Xiong2Dan Namarika3Albert Mwafongo4Michael Nyirenda5Loreen Chiwoko6Deborah Kamwendo7Irving Hoffman8Jeannette Lee9Sam Phiri10Wolfgang Vahrson11Blossom Damania12Dirk P. Dittmer13Center for Infectious Diseases and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USADepartment of Microbiology and Immunology, Curriculum in Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USAProgram in Global Oncology, Lineberger Comprehensive Cancer Center and Center for AIDS Research (CfAR), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USAKamuzu Central Hospital, Lilongwe, MalawiUNC Project, Lilongwe, MalawiLighthouse Trust, Lilongwe, MalawiUNC Project, Lilongwe, MalawiUNC Project, Lilongwe, MalawiCenter for Infectious Diseases and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USAUniversity of Arkansas for Medical Sciences, Little Rock, Arkansas, USAKamuzu Central Hospital, Lilongwe, MalawiGenedata, Basel, SwitzerlandProgram in Global Oncology, Lineberger Comprehensive Cancer Center and Center for AIDS Research (CfAR), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USAProgram in Global Oncology, Lineberger Comprehensive Cancer Center and Center for AIDS Research (CfAR), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.01633-14 |
| spellingShingle | 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 mBio |
| title | 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_short | Viral Profiling Identifies Multiple Subtypes of Kaposi’s Sarcoma |
| title_sort | viral profiling identifies multiple subtypes of kaposi s sarcoma |
| url | https://journals.asm.org/doi/10.1128/mBio.01633-14 |
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