Molecular Epidemiology and Characterization of K1, K15p and Orf75 Genes of Hhv-8 Associated With Hiv/aids Kaposi’s Sarcoma in Patients at Kenyatta National Hospital

Abstract

Background: Kaposi’s sarcoma is a lifelong persistant infection in human once exposed. Immunosupression due to HIV sets foundation for Kaposi’s sarcoma herpesvirus infection. Kaposi’s sarcoma overcomes cellular intrinsic immunity to initiate viral protein expression. The strength of the current study is that it brings new knowledge in understanding the biology of KS disease based on the expression of KSHV genes K1 and K15P which are known to modulate immune responses during disease progression and ORF75 which enhances lytic viral replication. Objective: To describe the molecular epidemiology and characterization of the selected HHV-8 genes associated with AIDS-KS at Kenyatta National Hospital, Kenya. Materials and methods: This was a hospital based descriptive cross-sectional study. The quantitative approach of data collection, analysis and presentation was used. The cases were traced following histological reports diagnosed as KS or KS-like between January 2013 and December 2016. Consecutive sampling technique was used to pick the cases from Kenyatta National Hospital. In total, 81 cases that met the inclusion criteria were studied. The laboratory test used to study the cases was histology, polymerase chain reaction and sequencing. A comprehensive bio-medical data linking the blocks was obtained from the registry records. The Statistical Package for Social Sciences (SPSS) version 21.0 where Logistic regression analysis, chi-square and t-test was used. A p value less than 0.05 was considered statistically significance. Results: Of the 81 cases studied, mean age was 39.3 (SD=9.5) years, range 19-63 years, mode 34 years, and median 38 years. Majority (48.2%) of the studied cases were in the age group of 30-39 years. Males were 46 (56.8%) and females 35 (43.2%). The ratio of males to females was 1:0.8. The mean difference in age between male and female cases was 2.9 years, t=1.3, p=0.10. The 81 studied cases, 49 (60.5%) had nodular KS lesions, while 19 (23.5%) and 13 (16.0%) were plaques, and patchy lesions respectively. Both K1 and K15P gene was demonstrated in 42 (91.3%) males and 30 (85.7%) females, OR=1.7(0.4-7.0), p=0.42. The ORF75 gene was identified in 28 (60.9%) males and 21 (60.0%) females, OR=1.0 (4.2-2.5), p=0.93. Discussion: During the height of HIV and AIDS, KS gained public attention and the manifestation of the lesions caused a lot of stigmatization among the affected patients. The introductionof antiviral therapy globally led to reduction in the number of KS cases, although KS is stilled observed in people with well-controlled HIV infection. In the current study, Kaposi’s sarcoma herpesvirus was highly prevalent in the studied cases who also had HIV. Although KS is associated with HIV and AIDS, KSHV has an infectious origin that is independent of HIV. A combination of KSHV and impaired host immunity causes Kaposi’s sarcoma. The findings on age and gender are different from published reports on the molecular epidemiology and characterization of KSHV. In the current study, the cases that had Kaposi’s sarcoma were young adults and male preponderance observed. The current study findings on molecular epidemiology and characterization showed that K1, K15P and ORF75 genes were predominantly among the male cases. The K1, K15P and ORF75 genes of Kaposi’s sarcoma overcomes cellular intrinsic immunity to initiate viral protein expression and genome replication in a primary infection. The nucleotide sequences of K1, K15P and ORF75 gene were aligned to other HHV8 gene sequences which have been deposited in the NCBI data bank (http://www.ncbi.nlm.nih.gov). Conclusion: Molecular epidemiology and characterization results showed that K1, K15P and ORF75 genes of KSHV were highly present in the studied cases. The nodular morphological subtype of KS was also predominant. Recommendation: Molecular technique should be adopted for the testing of KSHV because it permits better detection of the virus