Mouse Strain Differences in the Chemokine Response to Acute Lung Infection with a Murine Gammaherpesvirus

Weinberg, Jason B.; Lutzke, Mary L.; Alfinito, Rosiane S.; Rochford, Rosemary

doi:10.1089/088282404322875467

Cited by 42 publications

(36 citation statements)

References 44 publications

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“…Pertinent to our study, IFN-g has been shown to prevent EBV-induced B-cell transformation (18), and inhibit HHV-8 production (25), indicating that it likely plays an important role in human gammaherpesvirus infections. Another study reported differences in the immune response between C57BL/6 and BALB/C mice infected with MHV-68, with several differences seen in chemokine production (40). IFN-g was higher in BALB/C mice than C57BL/6 mice, but viral titers were also higher, indicating no correlation with increased resistance to infection (40).…”

Section: Discussionmentioning

confidence: 99%

“…Another study reported differences in the immune response between C57BL/6 and BALB/C mice infected with MHV-68, with several differences seen in chemokine production (40). IFN-g was higher in BALB/C mice than C57BL/6 mice, but viral titers were also higher, indicating no correlation with increased resistance to infection (40). Also, MHV-68-induced lymphomas in the absence of MHC class I-mediated immune surveillance preferentially occur in the BALB/C background (34).…”

Section: Discussionmentioning

confidence: 99%

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Strain-Dependent Requirement for IFN-γ for Respiratory Control and Immunotherapy in Murine Gammaherpesvirus Infection

Tsai¹,

Hu²,

Zhang³

et al. 2011

Viral Immunology

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Interferon-g (IFN-g) and perforin (pfp) are important effector mechanisms used by CD8 T cells to clear virusinfected cells. In this study, we used IFN-g/pfp double knockout mice to address if these two effector molecules play redundant roles in the control of acute infection with murine gammaherpesvirus-68 (MHV-68) in BALB/C mice. Perforin knockout (KO) mice and wild-type mice cleared infectious virus from the lungs, even following high-dose infection. However, the IFN-g KO and IFN-g/pfp double knockout (DKO) groups had higher virus titers in the lungs at day 10 post-infection, and both groups had higher mortality rates. In IFN-g/pfp DKO mice, the virus titer and mortality rate were significant higher than in IFN-g KO mice, indicating a role for perforin in protection from disease. WT mice given IFN-g blocking antibody also showed significantly higher viral titers. In contrast, IFN-g KO mice on a C57BL/6 background controlled respiratory infection comparably to wild-type mice. These data show that perforin plays a redundant role in the control of virus replication, but IFN-g plays an essential role in BALB/C mice infected with MHV-68. We conclude that there is a marked strain-dependent difference in the effector mechanisms needed to control acute MHV-68 infection between C57BL/6 and BALB/C mice. In addition we show that immune therapy that re-establishes viral control after spontaneous reactivation in CD4-deficient mice depends upon perforin in C57BL/6 mice but IFN-g in BALB/C mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Strain-Dependent Requirement for IFN-γ for Respiratory Control and Immunotherapy in Murine Gammaherpesvirus Infection

Tsai¹,

Hu²,

Zhang³

et al. 2011

Viral Immunology

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“…For the plaque assay, supernatants were aspirated off MEF monolayers and homogenate dilutions were plated in 1 ml complete DMEM. Plates were incubated for 2 h at 37 uC, and the plaque assay procedure was continued as described elsewhere (Weinberg et al, 2004). Titres are expressed as p.f.u.…”

Section: Methodsmentioning

confidence: 99%

“…All DNA extraction procedures were done from homogenized tissue lysates using the QIAamp DNA Mini kit (Qiagen). Real-time quantitative (Q)-PCR was performed using primers and probe against cHV-68 viral DNA as described elsewhere (Weinberg et al, 2004). Mouse bactin primers and probes have been described elsewhere (Schuetze et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

Infection of neonates with murine gammaherpesvirus 68 results in enhanced viral persistence in lungs and absence of infectious mononucleosis syndrome

Ptaschinski

Rochford

2008

Journal of General Virology

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We used the murine gammaherpesvirus 68 (γHV-68), which serves as a model for human gammaherpesvirus infection, to determine whether age at infection altered the pattern of gammaherpesvirus pathogenesis. We infected mice intranasally at 8 days old (pups) and 6 weeks old (adults) to investigate differences in γHV-68 pathogenesis. There was no difference between adults or pups in acute infection in the lungs at 6 days post-infection (p.i.). However, mice infected as pups exhibited a more disseminated viral infection with viral DNA detected in the spleen, liver and heart as measured by quantitative PCR (Q-PCR). In addition, viral DNA was detected in the lungs of mice infected as pups until 60 days p.i. Three viral transcripts (M2, M3 and M9) were expressed at both 30 and 60 days p.i. In contrast, no viral DNA or mRNA expression was detected in lungs of mice infected as adults at 30 or 60 days p.i. Mice infected as adults experienced a peak in latent infection in the spleen at 16 days p.i., corresponding with an increase in splenic weight and expansion of the Vβ4+ CD8+ T-cell population, similar to infectious mononucleosis observed following infection of young adults with Epstein–Barr virus. However, the increase in splenic weight of infected pups was not as pronounced and no significant increase in Vβ4+ CD8+ T-cell expansion was observed in infected pups. Together, these data suggest that the pathogenesis of murine gammaherpesvirus γHV-68 is age-dependent.

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“…Real-time quantitative PCR was performed using primers and probe against gHV-68 viral DNA as previously described (46). Mouse b-actin was used as an internal control with primers and probe as previously described (5).…”

Section: Dna Extraction and Real-time Quantitative Pcrmentioning

confidence: 99%

In VivoActivation of Toll-Like Receptor-9 Induces an Age-Dependent Abortive Lytic Cycle Reactivation of Murine Gammaherpesvirus-68

et al. 2010

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Infection of mice with murine gammaherpesvirus-68 (gHV-68) serves as a model to understand the pathogenesis of persistent viral infections, including the potential for co-infections to modulate viral latency. We have previously found that infection of neonates (8-day-old mice) with gHV-68 resulted in a high level of persistence of the virus in the lungs as well as the spleen, in contrast to infection of adult mice, for which long-term latency was only readily detected in the spleen. In this study we investigated whether stimulation of toll-like receptor (TLR)9 would modulate viral latency in mice infected with gHV-68 in an age-dependent manner. Pups and adult mice were injected with the synthetic TLR9 ligand CpG ODN at 30 dpi, at which time long-term latency has been established. Three days after CpG injection, the lungs and spleens were removed, and a limiting dilution assay was done to determine the frequency of latently infected cells. RNA was extracted to measure viral transcripts using a ribonuclease protection assay. We observed that CpG injection resulted in an increase in the frequency of latently-infected cells in both the lungs and spleens of infected pups, but only in the spleens of infected adult mice. No preformed virus was detected, suggesting that TLR9 stimulation did not trigger complete viral reactivation. When we examined viral gene expression in these same tissues, we observed expression only of the immediate early lytic genes, rta and K3, but not the early DNA polymerase gene or late gB transcript indicative of an abortive reactivation in the spleen. Additionally, mice infected as pups had greater numbers of germinal center B cells in the spleen following CpG injection, whereas CpG stimulated the expansion of follicular zone B cells in adult mice. These data suggest that stimulation of TLR9 differentially modulates gammaherpesvirus latency via an age-dependent mechanism.

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Mouse Strain Differences in the Chemokine Response to Acute Lung Infection with a Murine Gammaherpesvirus

Cited by 42 publications

References 44 publications

Strain-Dependent Requirement for IFN-γ for Respiratory Control and Immunotherapy in Murine Gammaherpesvirus Infection

Strain-Dependent Requirement for IFN-γ for Respiratory Control and Immunotherapy in Murine Gammaherpesvirus Infection

Infection of neonates with murine gammaherpesvirus 68 results in enhanced viral persistence in lungs and absence of infectious mononucleosis syndrome

In VivoActivation of Toll-Like Receptor-9 Induces an Age-Dependent Abortive Lytic Cycle Reactivation of Murine Gammaherpesvirus-68

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