Molecular epidemiology of the HHV-8 K1 gene from Moroccan patients with Kaposi's sarcoma

Abstract

The genetic variability of the human herpesvirus 8 (HHV-8) strains circulating in the populations living in the Maghreb region, an endemic area for HHV-8 and associated Kaposi's sarcoma, remains largely unknown. We have thus analyzed the genetic variation of the complete K1 gene of HHV-8 in a series of 35 viral strains, originating from 28 Moroccan patients with classic, AIDS-associated or iatrogenic Kaposi's sarcoma lesions. All but one of the 35 strains belonged to the large C molecular subtype. Furthermore, high genetic diversity within the C subtype was observed in the 35 sequenced HHV-8 K1 genes, with strains belonging to several and distinct subgroups highly supported from a phylogenetically viewpoint (e.g., C3, C7, C'' and C5). Considering these newly identified Moroccan viral strains in the context of 189 complete K1 genes, we were able to characterized, using the Simplot program, two main groups of recombinant chimeric K1 genes, either intertypic (C5) or intratypic (C7). In addition, the genetic characterization of the host maternal gene pool, through the analyses of mtDNA variation, did not provide evidence for any association between a particular human ethno-geographic background (i.e., North African vs. sub-Saharan African vs. West Eurasian linages) and any HHV-8 strain because both C' and C'' strains were randomly distributed among the different patients' population backgrounds.

Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma

“…With regard to the phylogenetic analysis, the genetic diversity present in the clade C of HHV-8 (C1, C2, C3, or C7) from non-KS patients was similar to that previously reported in a HHV-8 endemic African country, [49] including slowly progressing classic KS and intra-familial transmission in the Mediterranean countries. [8,14,50,51] On the other hand, there was a lack of diversity within clade C in the KS group, which was composed of 100% of HHV-8 subgenotype C3, (Tables 3 and 4).…”

“…Our data corroborate the previous study showing evidence of recombinant virus patterns C5 (A3 and C3) and C7 (C1 and C2/C3), which were described in classic and epidemic KS. [49] …”

“…In fact, most studies consistently demonstrate that co-infection by different HHV-8 genotypes is extremely rare, [26,46,50–52] thus supporting that the currently detected recombinant forms do not originate from new events, but they represent previous circulating recombinant forms. [2,49] …”

Epidemiology and Genetic Variability of HHV-8/KSHV in Pygmy and Bantu Populations in Cameroon

“…There are two highly variable K1 regions (VR1 and VR2), which encode the areas usually targeted by the immune system on the K1 protein [30], [41]. Subgroup A1–4 and subtype C are predominant among populations of European descent [30], [32], [36], [42], [43] and in some regions of Asia [44], [45], [46]. Subgroup B1–4 and clade A5 are predominant in Sub-Saharan Africa [31], [34], [35], [47], [48], [49], [50].…”

Human herpesvirus 8 infections in patients with immunodeficiencies

“…DNA sequence analysis of the K1 gene (coding for a glycoprotein) reveals important sequence polymorphisms that account for at least 30% amino acid variability. This polymorphism permits the classification of the virus in 4 distinct molecular variants (A,B,C,D) [27,28].…”