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J Gen Virol 67 (1986), 2605-2616; DOI 10.1099/0022-1317-67-12-2605
© 1986 Society for General Microbiology

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Human Cytomegalovirus Persistent Infection in a Human Central Nervous System Cell Line: Production of a Variant Virus with Different Growth Characteristics

Tsutomu Ogura1, Junji Tanaka1, Shigeru Kamiya2, Hiroshi Sato1, Hisashi Ogura1 and Motoichi Hatano1

1 Department of Virology, Cancer Research Institute, Kanazawa University, Kanazawa 920
and2 Department of Bacteriology, School of Medicine, Kanazawa University, Kanazawa 920, Japan

The susceptibility of human central nervous system cell lines to human cytomegalovirus (HCMV) and the fate of infected cultures were studied. Significant amounts of infectious progeny virus were produced in 118MGC glioma and IMR-32 neuroblastoma, but not in KGC oligodendroglioma cells when the cultures were infected with wild-type virus (HCMVwt) at an m.o.i. of 10 p.f.u. per cell. Further passage of infected 118MGC cells resulted in the establishment of a long-term persistent infection. This infection, designated 118MGC/Towne, continuously produced infectious virus (HCMVpi) with titres ranging from 102 to 105 p.f.u./106 cells up to 360 days post-infection (corresponding to 50 subcultures). Since no temperature-sensitive mutants, defective interfering particles or interferon-like activity were found in the 118MGC/Towne cultures, maintenance of the persistent infection seemed to be due to a balance between the release of infectious virus and the growth of uninfected cells. The HCMVpi produced in long-term persistently infected cultures was shown to be different from the HCMVwt originally used to infect by the following characteristics: (i) HCMVpi replicated slowly and yielded lower amounts of progeny virus than HCMVwt; (ii) HCMVpi induced a 73000 mol. wt. immediate early protein that was not synthesized in HCMVwt-infected cells; (iii) HCMVpi had a different DNA structure from that of HCMVwt. These results suggest that HCMVpi is a slower growing variant of HCMVwt and probably plays an important role in the maintenance of the persistent infection.

Keywords: HCMV, CNS cell line, persistent infection, variant virus

Received 29 April 1986; accepted 26 August 1986.


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