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Antigenic open reading frames from HHV-8 are present in multiple myeloma patients and normal individuals at similar
Yuan Xiao Zhu1, Zhi Hua Li, Michael Voralia
1Department of Medical Oncology, The Princess Margaret Hospital, Toronto General Hospital Research Institute, Ont., Canada.
Abstract:
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.
Insights
Human herpes virus 8 (HHV-8) DNA is frequently detected in multiple myeloma (MM) patients and healthy individuals using PCR. This study found no evidence of a specific HHV-8 strain deficiency in MM patients.
Area of Science:
- Virology
- Oncology
- Immunology
Background:
- Multiple myeloma (MM) patients often lack a detectable humoral response to human herpes virus 8 (HHV-8).
- This absence has been hypothesized to result from HHV-8 strain variation or mutations in antigenic regions.
- Previous studies relied on ELISA, potentially missing infections.
Purpose of the Study:
- To investigate the presence and genetic characteristics of HHV-8 in multiple myeloma (MM) patients.
- To determine if specific HHV-8 strains or mutations are associated with MM.
- To compare HHV-8 detection rates in MM patients versus healthy controls.
Main Methods:
- Nested PCR was used to detect HHV-8 DNA sequences in three antigenic regions (ORF65, ORF73, ORFK8.1) and the K1 ORF.
- Samples were analyzed from fresh bone marrow, bone marrow-derived dendritic cells (DCs), and bone marrow stromal cells (BMSCs) of 12 MM patients and 8 healthy individuals.
- Sequence analysis was performed on detected HHV-8 strains.
Main Results:
- HHV-8 ORFs were detected in a significant proportion of both MM patients (e.g., ORF65: 67%) and normal individuals (e.g., ORF65: 37%).
- HHV-8 sequences were more prevalent in cultured BMSCs and DCs from MM patients than in fresh bone marrow.
- No productive mutations in ORF65 were found in MM samples, and K1 sequences showed high homology to the K1-A1 strain, not a distinct MM-associated strain.
Conclusions:
- The data do not support the hypothesis of a specific K1-C3 HHV-8 strain with ORF65 deficiency in MM patients.
- HHV-8 infection is common in the general population when sensitive PCR methods are applied to multiple samples.
- The study highlights the limitations of serological assays for detecting HHV-8 in MM research.