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Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma: Is genotype B associated with better prognosis of AIDS-KS?

ABSTRACT: AIDS-associated Kaposi's sarcoma (AIDS-KS) caused by human herpes virus 8 (HHV-8) is the most severe and resistant form of KS tumor. Our aim was to verify whether there is an association between HHV-8 variability and development of AIDS-KS in Brazil by comparing the HHV-8 variability between individuals without and with KS. Saliva samples and blood, when available, were analyzed by polymerase chain reaction (PCR) techniques for detection of the fragments of ORF K1 of HHV-8, which were then genotyped and analyzed regarding the genetic variability. Our study described 106 positive cases for HHV-8 in the saliva from 751 AIDS patients without previous KS. In addition, we performed a phylogenetic analysis of HHV-8 in 34 of the 106 AIDS patients without KS and in 33 of the 37 patients with active KS. The distribution of HHV-8 genotypes A, B, C, and F in AIDS individuals was indistinguishable by comparing non-KS and KS groups, as well as regarding ethnicity. Considering the KS group, genotype B was associated with better prognosis of KS tumor. Interestingly, we found a particular profile of diversity within clade C and 2 recombinant patterns of HHV-8 in the saliva of AIDS individuals without KS. We emphasize the need to achieve standard genotyping protocol for ORF K1 amplification, thus allowing for substantial detection of HHV-8 variants. Our findings can shed light on the role of HHV-8 variability in the pathogenesis of AIDS-KS.

SUBMITTER: Tozetto-Mendoza TR

PROVIDER: S-EPMC5134807 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma: Is genotype B associated with better prognosis of AIDS-KS?

Tozetto-Mendoza Tania Regina TR Ibrahim Karim Yaqub KY Tateno Adriana Fumie AF de Oliveira Cristina Mendes CM Sumita Laura Massami LM Sanchez Maria Carmem Arroyo MCA Luna Expedito José EJ Pierrotti Ligia Camara LC Drexler Jan Felix JF Braz-Silva Paulo Henrique PH Pannuti Claudio Sérgio CS Romano Camila Malta CM

Medicine 20161101 48

AIDS-associated Kaposi's sarcoma (AIDS-KS) caused by human herpes virus 8 (HHV-8) is the most severe and resistant form of KS tumor. Our aim was to verify whether there is an association between HHV-8 variability and development of AIDS-KS in Brazil by comparing the HHV-8 variability between individuals without and with KS. Saliva samples and blood, when available, were analyzed by polymerase chain reaction (PCR) techniques for detection of the fragments of ORF K1 of HHV-8, which were then genot ...[more]

PMID: 27902590

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Project description:BackgroundKaposi sarcoma-associated herpes virus (KSHV) is one of the most common causal agents of Kaposi Sarcoma (KS) in individuals with HIV-infections. The virus has gained attention over the past few decades due to its remarkable pathogenic mechanisms. A group of genes, ORF71, ORF72, and ORF73, are expressed as polycistronic mRNAs and the functions of ORF71 and ORF72 in KSHV are already reported in the literature. However, the function of ORF73 has remained a mystery. The aim of this study is to conduct comprehensive exploratory experiments to clarify the role of ORF73 in KSHV pathology and discover markers of AIDS-associated KSHV-induced KS by bioinformatic approaches.Methods and resultsWe searched for homologues of ORF-73 and attempted to predict protein-protein interactions (PPI) based on GeneCards and UniProtKB, utilizing Position-Specific Iterated BLAST (PSI-BLAST). We applied Gene Ontology (GO) and KEGG pathway analyses to identify highly conserved regions between ORF-73 and p53to help us identify potential markers with predominant hits and interactions in the KEGG pathway associated with host apoptosis and cell arrest. The protein p53 is selected because it is an important tumor suppressor antigen. To identify the potential roles of the candidate markers at the molecular level, we used PSIPRED keeping the conserved domains as the major parameters to predict secondary structures. We based the FUGE interpretation consolidations of the sequence-structure comparisons on distance homology, where the score for the amino acids matching the insertion/deletion (indels) detected were based on structures compared to the FUGE database of structural profiles. We also calculated the compatibility scores of sequence alignments accordingly. Based on the PSI-BLAST homologues, we checked the disordered structures predicted using PSI-Pred and DISO-Pred for developing a hidden Markov model (HMM). We further applied these HMMs models based on the alignment of constructed 3D models between the known structure and the HMM of our sequence. Moreover, stable homology and structurally conserved domains confirmed that ORF-73 maybe an important prognostic marker for AIDS-associated KS.ConclusionCollectively, similar variants of ORF-73 markers involved in the immune response may interact with targeted host proteins as predicted by our computational analysis. This work also suggests the existence of potential conformational changes that need to be further explored to help elucidate the role of immune signaling during KS towards the development of therapeutic applications.

Dataset Information

Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma: Is genotype B associated with better prognosis of AIDS-KS?

Publications

Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma: Is genotype B associated with better prognosis of AIDS-KS?

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