The role of human herpesvirus-8 in the pathogenesis of multiple myeloma.
Human herpesvirus-8 has been strongly implicated in the pathogenesis of KS, BCBL, and multicentric Castleman's disease. Evidence for its role in the pathogenesis of multiple myeloma is accumulating. Human herpesvirus-8 is detectable in the nonmalignant bone marrow dendritic cells from most myeloma patients. In addition, HHV-8 is also detected in the peripheral blood of most myeloma patients. In contrast, this virus is rarely detected in close contacts of myeloma patients, healthy individuals, or patients with other malignancies. Furthermore, only about one fourth of patients with MGUS are infected with HHV-8. Sequencing of HHV-8 DNA isolated from myeloma patients shows both minor differences among patients and a conserved deletion unique to myeloma compared with HHV-8 in other malignancies. Consistent expression of both the viral homologues of IRF and IL-8R in myeloma suggests a possible role for these transforming viral genes in the pathogenesis of this disease. Although the described association between multiple myeloma and HHV-8 implies a causal role in the pathogenesis of this disease, no cause-and-effect relationship is yet demonstrated. Evidence may be obtained directly by fulfilling Koch's postulate in an animal model and indirectly through therapeutic interventions with antiviral agents or through extensive epidemiological studies. Such epidemiological studies would be greatly facilitated by the development of antibodies directed against the HHV-8 viral proteins uniquely present in myeloma. A direct or indirect causal effect of HHV-8 has potentially enormous implications for the therapeutic benefit of antiviral agents and preventative strategies using vaccines. There is, indeed, preliminary evidence that antiviral therapy in HIV-infected patients reduces the risk or development of KS. Clinical improvement in patients with KS treated with antiviral agents has also been reported. These observations suggest that future treatment strategies to combat multiple myeloma may include antiviral agents.
Sjak-Shie
N N
NN
Division of Hematology and Oncology, University of California School of Medicine, Los Angeles, USA.
Vescio
R A
RA
Berenson
J R
JR
D000914:Antibodies, Viral / Q000097:blood; D001853:Bone Marrow / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D006566:Herpesviridae Infections / Q000635:transmission / Q000821:virology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D009101:Multiple Myeloma / Q000821:virology*; D012514:Sarcoma, Kaposi; D012749:Sexually Transmitted Diseases
D000914:Antibodies, Viral; D004279:DNA, Viral