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.

Figure 1

Phylogenetic tree. (A) HHV-8 K1 midpoint-rooted maximum likelihood (ML) tree based on the present study samples (bold) and the HHV8-K1 reference sequences using GTR + 4 Γ nucleotide substitution model. Support values after 1000 bootstrap runs are shown for each node. Only bootstrap values above 70 supporting each branch are shown. (B) Projection of the samples of HHV-8 VR1 and VR2 (bold) onto the scaffold of the HHV8 K1 ML tree using the evolutionary placement algorithm approach. There were 52 HHV-8 K1 sequences from other worldwide studies (GenBank references: http://www.ncbi.nlm.nih.gov/): AF178794 (25Cas), AF133038 (BCBLR), FJ884626 (US216), AF130305 (Ema7), AF178786 (17Fuj), AF178807(K1-40/Bc1US), AF178799 (K1-32/Bcb), AF133039 (BCBLB), AF130282 (1IFe1I), AF130284 (IFe5I), AF178823 (58sar), AF133040 (31 KAP), AF130290 (Ug52U), AF130301 (UKma24), AF178782 (K1-11), AF178783 (K1-12), AF178791 (K1-22/Yan), AF178796 (K1-27), AF178801 (K1-34/E40), AF171056 (9/Tim), AF178792 (K1-23/Kok), AF178787 (K1-18Hec), AF178804 (K1-37/E44), AY042940 (MP5Z), AF178825 (K1-60/Ced), AF278843 (10/Bid/J21), AF130274 (cam1), AF201851 (8RU), N1394068, AF130267 (G17), DQ394055 (D19), AF133041(ASM72US), DQ394048 (D13), DQ394058 (I4), AF133042 (BC2US), DQ394044 (D10-1), DQ394049 (D14-1), DQ394060 (I7), AF148805 (GK18), DQ394038 (D4-2), DQ394064 (I10), AF130304 (UKma8), AF278846 (TKS10), AF133044 (ZKS3PF), AY329027 (HUA1), AY329028 (HUA2), AF220292 (Tupi1BR), AF220293 (Tupi2BR) and AF178810 (K1-43/Berr). Taxa plus “BR” indicate the code of nucleotide sequences from this study. Codes BR36 to BR68 indicate nucleotide sequence from the non-KS group, and codes BR01_KS to BR33_KS indicate nucleotide sequences from the KS group. Taxa in gray area indicate HHV-8 sequences obtained from different blood samples or matched blood (indicated by “_b”) and saliva (indicated by “_s”) for the same individual. HHV-8 = human herpesvirus type 8, KS = Kaposi's sarcoma, ML = maximum likelihood.