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.
Zhu
Yuan Xiao
YX
Department of Medical Oncology, The Princess Margaret Hospital, Toronto General Hospital Research Institute, Ont., Canada.
Li
Zhi Hua
ZH
Voralia
Michael
M
Stewart
A Keith
AK
D000956:Antigens, Viral / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D015994:Incidence; D009101:Multiple Myeloma / Q000473:pathology / Q000821:virology*; D016366:Open Reading Frames; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D000956:Antigens, Viral; D004279:DNA, Viral