HHV8 a subtype is associated with rapidly evolving classic Kaposi's sarcoma

Abstract

The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real-time PCR, an in-house developed IFA assay, and sequence analysis of ORF K1-VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p = 0.006 and p = 0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III-IV compared to stages I-II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A-supported infection.

Figure 1

Radial unrooted phylogenetic tree of 24 partial VR1 DNA sequences (348 bp) obtained from cKS italian patients. Neighbour joining (NJ) analysis with 100 bootstrap replicas was carried out including the following KHSV DNA sequences deposited in Genebank : A1: AF133038 A2:AF130305 A3: U86667 A4: AF133039 A5: AF178823; B1:AF133040; B2: AF130259 C1: AF133041 C3:AF133042; D1: AF133043 D2: AF133044 ;E:AF220292). Bootstrap values ≥ 70 are shown for support. Sequences highlighted in gray correspond to strain obtained from patients with slow evolution of cKS. 254×190mm (96 × 96 DPI)

Figure 2

KHSV A and C subtypes frequency (%) in cKS patients with slow and fast evolution. 254×190mm (96 × 96 DPI)