title: A gammaherpesviral internal repeat contributes to latency amplification.
abstract: BACKGROUND
  Gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. The genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood.
  
  
  RESULTS
  We used infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68) to explore the biological role of the 40 bp internal repeat of MHV-68. We constructed several mutant viruses partially or completely lacking this repeat. Both in vitro and in vivo, the loss of the repeat did not substantially affect lytic replication of the mutant viruses. However, the extent of splenomegaly, which is associated with the establishment of latency, and the number of ex vivo reactivating and genome positive splenocytes were reduced. Since the 40 bp repeat is part of the hypothetical open reading frame (ORF) M6, it might function as part of M6 or as an independent structure. To differentiate between these two possibilities, we constructed an N-terminal M6STOP mutant, leaving the repeat structure intact but rendering ORF M6 unfunctional. Disruption of ORF M6 did neither affect lytic nor latent infection. In contrast to the situation in lytically infected NIH3T3 cells, the expression of the latency-associated genes K3 and ORF72 was reduced in the latently infected murine B cell line Ag8 in the absence of the 40 bp repeat.
  
  
  CONCLUSIONS
  These data suggest that the 40 bp repeat contributes to latency amplification and might be involved in the regulation of viral gene expression.
authors: Institute of Molecular Immunology, Clinical Cooperation Group Hematopoietic Cell Transplantation, GSF National Research Center for Environment and Health, Munich, Germany.
authors: Nagendra N
authors: NN
authors: Thakur
authors: Susanne
authors: S
authors: El-Gogo
authors: Beatrix
authors: B
authors: Steer
authors: Klaus
authors: K
authors: Freimüller
authors: Andreas
authors: A
authors: Waha
authors: Heiko
authors: H
authors: Adler
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D041681:NIH 3T3 Cells; D016366:Open Reading Frames; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D018144:Rhadinovirus / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000473:pathology / Q000821:virology; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D017735:Virus Latency / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D014764:Viral Proteins
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