title: Analysis of genomic homology of murine gammaherpesvirus (MHV)-72 to MHV-68 and impact of MHV-72 on the survival and tumorigenesis in the MHV-72-infected CB17 scid/scid and CB17+/+ mice.
abstract: Murine gammaherpesvirus (MHV)-68-infected mice are well-known as models for Epstein-Barr virus (EBV)-related lymphoproliferative diseases. MHV-72 may be a relative of MHV-68, but any genetic comparison between the two (except for the M7 gene) has never been reported. The genetic compositions of MHV-72 and MHV-68 were compared and the pathology of MHV-72 infection studied in CB-17 severe combined immunodeficiency (scid/scid; SCID) and CB17 wild-type (CB17+/+) mice. The MHV-72 DNA sequence was almost identical to MHV-68 except for approximately 7000 bp corresponding to the MHV-68 M1-M3 genes. Twenty-seven of 30 MHV-72-infected SCID mice (90%) died from generalized infection with intranuclear viral inclusions for approximately 1 month, while MHV-72-infected CB17+/+ mice recovered from acute infection. Long observation and pathological study of 68 MHV-72-infected mice for up to 24 months revealed that the survival rate (29.4%) and survival time (21.3 months) of MHV-72-infected CB17+/+ mice were significantly lower (P = 0.0127) and shorter (P = 0.0065) than those of the controls (61.1% and 22.9 months), respectively. The malignancy development rate (60.3%) of the infected CB17+/+ mice was also significantly higher (P = 0.004) than those of the controls (22.2%). However, no MHV-72 DNA was detected in the tumors of infected mice. MHV-72 may have some tumor-promoting effects but the tumorigenesis in infected CB17+/+ mice is different from EBV-associated tumors.
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Oda
authors.forename: Jela
authors.initials: J
authors.lastname: Mistrikova
authors.forename: Marta
authors.initials: M
authors.lastname: Stancekova
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Dutia
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Nash
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahata
authors.forename: Zaishun
authors.initials: Z
authors.lastname: Jin
authors.forename: Takashi
authors.initials: T
authors.lastname: Oka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D018142:Gammaherpesvirinae / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D016679:Genome, Viral; D006566:Herpesviridae Infections / Q000276:immunology / Q000401:mortality / Q000821:virology*; D017403:In Situ Hybridization; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis; D012689:Sequence Homology, Nucleic Acid; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015996:Survival Rate; D014412:Tumor Virus Infections / Q000276:immunology / Q000401:mortality / Q000821:virology*
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D012367:RNA, Viral