Cmv-1, a genetic locus that controls murine cytomegalovirus replication in the spleen.

Scalzo, Anthony A.; Fitzgerald, N.A.; Simmons, Anthony; Vista, A B La; Shellam, Geoffrey

doi:10.1084/jem.171.5.1469

Cited by 276 publications

(213 citation statements)

References 33 publications

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“…54 A similar infectious dose response for CMV with the murine NK cell receptor Ly49 H has also been observed. 55,56 Together with the observation that essentially all significant associations were seen in lowdose IVDUs who happen to be African American in this study, our results support further evaluation of variants at IL10, IL19, and IL20 in HCV clearance.…”

Section: Discussionsupporting

confidence: 83%

Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

et al. 2005

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Hepatitis C virus (HCV) is an infectious blood-borne pathogen that usually persists as a chronic infection. However, approximately 15% of the time, patients can clear the virus, indicating that host differences could be critical in determining the course of HCV infection. The inflammatory response is crucial to resolving or failing to resolve an acute HCV infection. Some previous reports have implicated interleukin 10 (IL10) polymorphisms with successful anti-HCV therapy and natural viral clearance. We tested 54 single nucleotide polymorphisms (SNPs) in the IL10 region (7300 kb and 24 within the IL10 gene itself), which contains 13 genes including the IL10 immunomodulatory paralogs IL19, IL20, and IL24, for association with HCV clearance vs persistence. SNPs from two haplotype block regions, one at IL10 and the other from IL19/IL20, were associated with HCV clearance in African Americans (91 clearance cases and 183 chronically infected matched controls; P ¼ 0.05-0.002) while with expectation-maximization algorithm-reconstructed haplotypes, these associations remained (P ¼ 0.05-0.002). However, no significant associations were detected in European Americans (108 clearance and 245 chronic). Our results indicate that variants of the immunomodulatory IL10 and IL19/IL20 genes may be involved in natural clearance of HCV in the African-American population.

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Section: Discussionsupporting

confidence: 83%

Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

et al. 2005

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“…Similarly, the sequence data confirm the absence of a Ly49h-related gene in BALB/c mice as previously suggested by the lack of a NK cell subset staining with Ly49H-specific antibodies and the increased splenic viral titer of BALB/c mice relative to B6 during MCMV infection. 5,26,27 Furthermore, the complete sequencing of the BALB/c Ly49 cluster indicates that the 5E6 mAb should only recognize Ly49C on NK cells in this inbred strain since the BALB/c allele for Ly49i is a pseudogene. Thus, the BALB/c mouse strain is superior to B6 in this respect, as all functional NK studies performed with B6 mice using the 5E6 antibody cannot differentiate between the contributions of Ly49C and I.…”

Section: Discussionmentioning

confidence: 99%

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

Dewar

Ml³

et al. 2005

Genes Immun

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The BALB/c inbred mouse is widely used in models of infectious disease, transplantation, and cancer. The differences in the immune responses of BALB/c compared to C57BL/6 mice are especially valuable for the identification of immune regulation genes. One striking immune variance between these mice is in the function of natural killer (NK) cells, and there is strong evidence implicating differential expression of Ly49 genes. In this study, the complete BALB/c Ly49 gene cluster has been sequenced and found to contain six functional genes and two pseudogenes. Compared to C57BL/6 mice, there is a 200 kb region absent in the BALB/c cluster including a complete lack of Ly49h-related genes, which explains the increased susceptibility of BALB/c to cytomegalovirus infection. In addition, there is no BALB/c Ly49d allele, explaining the inability of BALB/c NK cells to kill certain tumor cells. The Ly49 region has now been sequenced in three different inbred mouse strains, and comparisons indicate that the evolution of each haplotype is not straightforward and has involved large-scale deletions/ insertions, gene recombination, and unequal crossing over between divergent haplotypes. This study confirms that relatively small murine class I MHC receptor haplotypes exist, analogous to observations made of human killer cell Ig-like receptor gene haplotypes.

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“…C57BL/6 mice exhibit lower viral titers in tissues than BALB/c mice after primary infection (Chalmer et al, 1977;Grundy et al, 1981;Scalzo et al, 1990), and thus lower anti-viral antibody responses to wild type virus could simply reflect a lower viral antigen load. To eliminate this possibility, we utilized a second strain of MCMV with deletion of gene m157.…”

Section: Humoral Responses Have Been Fairly Well Characterized Bmentioning

confidence: 99%

“…Work by Jonic et al using B-cell deficient mice clearly supports the hypothesis that humoral responses are dispensable during primary MCMV infection (Jonjic et al, 1994), but B-cell knockout mice used in these studies had a C57BL/6 background. C57BL/ 6 mice have well described alternative pathways to control MCMV Rodriguez et al, 2004;Scalzo et al, 1990), and therefore extrapolating these results to BALB/c mice might be inappropriate. It is therefore possible that antibody responses in BALB/ c mice are more important in viral control than in C57BL/6 mice.…”

Section: Humoral Responses Have Been Fairly Well Characterized Bmentioning

confidence: 99%

A flow cytometry-based method for detecting antibody responses to murine cytomegalovirus infection

Bickerstaff

Zimmerman

Wing

et al. 2007

Journal of Virological Methods

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An assay based on target cells infected with green fluorescent protein labeled murine cytomegalovirus (GFP-MCMV) and dual color flow cytometry for detecting antibody to MCMV is described. After optimizing conditions for this technique, kinetics of anti-MCMV IgG antibody response were tested in susceptible (BALB/c) and resistant (C57BL/6) mouse strains following primary MCMV infection. Previously published antibody kinetics were confirmed in susceptible mice, with peak IgG response seen ~8 weeks after primary infection, decreasing by 20 weeks after infection. In contrast, MCMV resistant C57BL/6 mice showed significantly lower IgG antibody responses than susceptible mice. Although several techniques have been previously described to detect murine antibody responses to MCMV, including nuclear anti-complement immunofluorescence, viral immunoblotting, complement fixation, indirect immunofluorescence, indirect hemagglutination, and enzyme-liked immunosorbent assay techniques, these techniques are all time consuming and laborious. The technique presented is a simple time efficient alternative to detect previous MCMV antibody responses in experimentally infected mice.

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Cmv-1, a genetic locus that controls murine cytomegalovirus replication in the spleen.

Cited by 276 publications

References 33 publications

Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

A flow cytometry-based method for detecting antibody responses to murine cytomegalovirus infection

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