Human cytomegalovirus protects multiple myeloma cell line KM3 cells from apoptosis induced by growth factor withdrawal.
BACKGROUND
There is a higher rate of cytomegalovirus (CMV) reactivation in patients with multiple myeloma after an autologous stem cell transplantation, but no attention has been given thus far to a possible pathogenetic interplay between CMV and multiple myeloma. CMV can infect many kinds of cells, and CMV infection has been shown to inhibit apoptotic responses in several cell systems. In this study the authors investigated the alterations in apoptosis in the multiple myeloma cell line KM3 after infection with CMV and proposed a possible mechanism.


METHODS
KM3 cells were infected with 100, 10, or 1 TCID50 of CMV and then cultured in serum-free RPMI 1640. An RT-PCR-based assay was used to detect mRNA expression of CMV-IE, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and IL-6 in CMV-infected and mock-infected cells. Flow cytometry was used to detect apoptotic cells. CMV particles and apoptotic cells were also examined with an electron microscope.


RESULTS
CMV-infected KM3 cells clearly expressed immediate early (IE) antigen mRNA when compared to uninfected cells, and there were fewer apoptotic cells among cells treated with 100 or 10 TCID50 of CMV after culturing in serum-free RPMI 1640. CMV particles were observable in infected cells under an electron microscope. Expression of IL-6 mRNA increased after infection.


CONCLUSIONS
CMV can infect the multiple myeloma cell line KM3, inhibit the apoptotic response in these cells after apoptosis induction in serum-free culture, and increase the expression of IL-6 mRNA.
Wei
Guo-qing
GQ
Department of Hematology, First Affiliated Hospital, College of Medical Sciences, Zhejiang University, Hangzhou 310003, China. weiguoqing2000@hotmail.com
Lin
Mao-fang
MF
Huang
He
H
Cai
Zhen
Z
D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D009101:Multiple Myeloma / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D014764:Viral Proteins / Q000032:analysis
D017874:Immediate-Early Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D014764:Viral Proteins