Comparative transcriptome analysis of endemic and epidemic Kaposi’s sarcoma (KS) lesions and the secondary role of HIV-1 in KS pathogenesis
| Autor: | For Yue Tso, Salum J. Lidenge, Julius Mwaiselage, Andrew V. Kossenkov, Owen Ngalamika, John R. Ngowi, Jayamanna Wickramasinghe, Paul M. Lieberman, Sara R. Privatt, John T. West, Charles E. Wood |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
RNA viruses
Male Gene Expression HIV Infections medicine.disease_cause Pathology and Laboratory Medicine Transcriptome Pathogenesis Kaposi Sarcoma Medical Conditions Immunodeficiency Viruses Medicine and Health Sciences Biology (General) 0303 health sciences Coinfection 030302 biochemistry & molecular biology Sarcoma Genomics Kaposi's Sarcoma-Associated Herpesvirus Middle Aged Infectious Diseases Oncology Medical Microbiology Viral Pathogens Viruses Herpesvirus 8 Human Female medicine.symptom Pathogens Transcriptome Analysis Research Article Adult Herpesviruses Patients QH301-705.5 Immunology Inflammation Biology Microbiology 03 medical and health sciences Young Adult Immune system Signs and Symptoms Virology Retroviruses medicine Genetics Humans Kaposi's sarcoma-associated herpesvirus Molecular Biology Gene Microbial Pathogens Sarcoma Kaposi 030304 developmental biology Tumor microenvironment Gene Expression Profiling Lentivirus Organisms Biology and Life Sciences HIV Computational Biology Cancers and Neoplasms RC581-607 Genome Analysis Health Care Co-Infections HIV-1 Lesions Parasitology Immunologic diseases. Allergy Clinical Medicine Carcinogenesis DNA viruses |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 16, Iss 7, p e1008681 (2020) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | In sub-Saharan Africa, endemic Kaposi’s sarcoma (EnKS) is still prevalent despite high incidence of epidemic Kaposi’s sarcoma (EpKS) resulting from the on-going HIV-1 epidemic. While KSHV is clearly the etiologic agent of KS, the mechanisms underlying KS development are not fully understood. For example, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in EpKS remains unclear. How, or whether, EpKS is mechanistically distinct from EnKS is unknown. Thus, the absence of HIV-1 co-infection in EnKS provides a unique control for investigating and deciphering whether HIV-1 plays a direct or indirect role in the EpKS tumor microenvironment. We hypothesized that HIV-1 co-infection would induce transcriptome changes that differentiate EpKS from EnKS, thereby defining the direct intra-tumor role of HIV-1 in KS. Comparison of ART-treated and -naïve patients would further define the impact of ART on the KS transcriptome. We utilized RNA-seq followed by multiparameter bioinformatics analysis to compare transcriptomes from KS lesions to uninvolved control skin. We provide the first transcriptomic comparison of EpKS versus EnKS, ART-treated vs–naïve EpKS and male vs female EpKS to define the roles of HIV-1 co-infection, the impact of ART, and gender on KS gene expression profiles. Our findings suggest that ART-use and gender have minimal impact on transcriptome profiles of KS lesions. Gene expression profiles strongly correlated between EpKS and EnKS patients (Spearman r = 0.83, p Author summary Despite improved antiretroviral therapy (ART) coverage, Kaposi’s sarcoma (KS) remains the most common cancer in people living with HIV/AIDS. KSHV is known to cause KS, but there are no preventive or curative vaccines. Our understanding of the interactions between KSHV, host cell and the microenvironment is lacking. HIV-1 co-infection has been implicated in KS pathogenesis, but its mechanistic role is unclear. We analyzed transcriptomes from lesions and uninvolved control skin from HIV-1-positive and -negative KS patients to determine the direct or indirect role of HIV-1 in KS development. Transcriptomes from the uninvolved control skin from KS subjects were indistinguishable from that of non-KS healthy individuals. This validates the use of uninvolved control skin to control for gene expression pattern in KS lesions. Despite high concordance in gene expression profiles between HIV-1-positive and -negative KS patients, a subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude of dysregulation in EnKS than EpKS patients. The trend toward lower magnitude of gene dysregulation in EpKS coupled with the absence of HIV-1-transcripts in EpKS suggests an indirect or systemic effect of HIV-1 to promote KS tumorigenesis and possibly explain the high KS incidence in regions with endemic KSHV and HIV-1 co-infections. |
| Databáze: | OpenAIRE |
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