Antigenic open reading frames from HHV-8 are present in multiple myeloma patients and normal individuals at similar frequency

It has been proposed that the absence of a humoral response to human herpes virus 8 (HHV-8) in patients with multiple myeloma (MM) reflects strain variation or the mutation, or absence, of the antigenic regions of HHV-8 recognized in ELISA screening tests. We therefore assessed DNA sequence of three antigenic regions (ORF65, ORF73 and ORFK8.1) and the transforming hypervariable K1 ORF of HHV-8 in fresh bone marrow cells, bone marrow derived dendritic cells (DCs) and bone marrow stromal cells (BMSCs) from 12 patients with MM and 8 normal individuals. HHV-8 ORFs were detectable by nested PCR in MM patients (ORF65: 67% ORF73: 22% and K8.1: 58%), but were also surprisingly frequent in normal individuals (ORF65: 37%, ORF73: 12.5% and K8.1: 62%). HHV-8 sequences were more frequently detected in cells from BMSC and DC culture than from fresh bone marrow in MM. In contrast no HHV-8 sequences were detected in BMSC from normal individuals. Sequence analysis of ORF65 failed to demonstrate productive mutations in any MM sample. K1 genomic sequences were detected in 42% of MM and 37% of normals and exhibited 98% homology with the K1-A1 HHV-8 strain. In conclusion, our data do not support the presence of a K1-C3 strain of HHV-8 with ORF65 expression deficiency in MM patients. HHV-8 infection appears to be common in the general population when sensitive PCR is employed and multiple samples are analyzed.