T-Cell Responses to the M3 Immune Evasion Protein of Murid Gammaherpesvirus 68 Are Partially Protective and Induced with Lytic Antigen Kinetics

Obar, Joshua J.; Donovan, Douglas C.; Crist, Sarah G.; Silvia, O.J.; Stewart, James P.; Usherwood, Edward J.

doi:10.1128/jvi.78.19.10829-10832.2004

Cited by 13 publications

(8 citation statements)

References 32 publications

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“…T cell subpopulations were depleted by i.p. injection of 500 µg of either control Rat IgG, anti-CD4 antibody (GK1.5), anti-CD8 antibody (TIB210), or both anti-CD4/CD8 antibody on days -3, -2, -1, 0 then every other day until day 21 post challenge (32). On Day 0 of antibody treatment T cell depletion was confirmed and mice were i.p.…”

Section: Methodsmentioning

confidence: 99%

Cell-Mediated Immunity toToxoplasma gondiiDevelops Primarily by Local Th1 Host Immune Responses in the Absence of Parasite Replication

Gigley

Fox

Bzik

2009

The Journal of Immunology

120

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A single inoculation of mice with the live, attenuated Toxoplasma gondii uracil auxotroph strain cps1-1 induces long-lasting immunity against lethal challenge with hypervirulent strain RH. The mechanism for this robust immunity in the absence of parasite replication has not been addressed. The mechanism of long-lasting immunity, the importance of route of immunization, cellular recruitment to the site of infection, and local and systemic inflammation were evaluated. Our results show that infection with cps1-1 elicits long-lasting CD8+ T cell- mediated immunity. We show that immunization with cps1-1-infected dendritic cells elicits long-lasting immunity. Intraperitoneal infection with cps1-1 induced a rapid influx of GR1+ neutrophils and two stages of GR1+CD68+ inflammatory monocyte infiltration into the site of inoculation. CD19+ B cells and CD3+ T cells steadily increase for 8 days after infection. CD8+ T cells were rapidly recruited to the site of infection and increased faster than CD4+ T cells. Surprisingly, cps1-1 infection induced high systemic levels of bioactive IL-12p70 and a very low level and transient systemic IFN-γ. Furthermore, we show significant levels of these inflammatory cytokines were locally produced at the site of cps1-1 inoculation. These findings offer new insight into immunological mechanisms and local host responses to a non-replicating type I parasite infection associated with development of long-lasting immunity to Toxoplasma gondii.

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Section: Methodsmentioning

confidence: 99%

Cell-Mediated Immunity toToxoplasma gondiiDevelops Primarily by Local Th1 Host Immune Responses in the Absence of Parasite Replication

Gigley

Fox

Bzik

2009

The Journal of Immunology

120

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“…Furthermore, MHV-68 has provided a tractable model to examine the efficacy of various vaccine strategies for gammaherpesviruses. Peptide and subunit vaccination targeting lytic and latency-associated viral proteins reduces acute infection in the lungs and peak latency in the spleens of laboratory mice (37,46,55,57,65,73). Similar effects have also been demonstrated for a vaccine based on heat-inactivated MHV-68 (1).…”

mentioning

confidence: 49%

Induction of Protective Immunity against Murine Gammaherpesvirus 68 Infection in the Absence of Viral Latency

Jia¹,

Freeman

Yager

et al. 2010

J Virol

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Human gammaherpesviruses, Epstein-Barr virus, and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus are important pathogens associated with diseases, including lymphomas and other malignancies. Murine gammaherpesvirus 68 (MHV-68) is used as an experimental model system to study the host immune control of infection and explore novel vaccine strategies based on latency-deficient live viruses. We studied the properties and the potential of a recombinant MHV-68 (AC-RTA) in which the genes required for persistent infection were replaced by a constitutively expressed viral transcription activator, RTA, which dictates the virus to lytic replication. After intranasal infection of mice, replication of AC-RTA in the lung was attenuated, and no AC-RTA virus or viral DNA was detected in the isolated splenocytes, indicating a lack of latency in the spleen. Infection of the AC-RTA virus elicited both cellular immune responses and virus-specific IgG at a level comparable to that elicited by infection of the wild-type virus. Importantly, vaccination of AC-RTA was able to protect mice against subsequent challenge by the wild-type MHV-68. AC-RTA provides a vaccine strategy for preventing infection of human gammaherpesviruses. Furthermore, our results suggest that immunity to the major latent antigens is not required for protection.

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“…M3 is an example of a soluble chemokine modulator acting as immune evasion tool. DNA vaccination of mice with an M3 expressing plasmid yielded partial protection lowering the infectious virus titre in the lungs of challenged animals [66]. The latter authors showed that M3 elicited a cytotoxic T cell response during acute infection, which persisted at later stages of latency.…”

Section: Virus Strainmentioning

confidence: 79%

Comparison of pathogenic properties of the murid gammaherpesvirus (MuHV 4) strains: a role for immunomodulatory proteins encoded by the left (5′-)end of the genome

Mistríková¹,

Rajčáni

2008

Open Life Sciences

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Abstract:The murid herpesvirus 4 (MuHV 4) species encompasses 7 isolates, out of which at least two (MHV-68, MHV-72) became in vitro propagated laboratory strains. Following intranasal inoculation, MuHV 4 induces an acute infectious mononucleosis-like syndrome with elevated levels of peripheral blood leukocytes, shifts in the relative proportion of lymphocytes along with the appearance of atypical mononuclear cells. At least two isolates exhibited spontaneous deletions at the left hand (5´-end) of their genome, resulting in the absence of M1, M2, M3 genes (strain MHV-72) and also of the M4 gene (strain MHV-76). Based on DNA sequence amplifications only, another two isolates (MHV-Šum and MHV-60) were shown to possess similar deletions of varying length. During latency (until 24 months post-infection), the mice infected with any MuHV 4 isolate (except MHV-76) developed lymphoproliferative disorders. The lack of tumor formation in MHV-76 infected mice was associated with persistent virus production at late post-infection intervals. In addition to careful analysis of spontaneously occurring 5´-end genome defects, our knowledge of the function of 5´-end genes relies on the behaviour of mutants with corresponding deletions and/or insertions. While M2 and M3 genes encode immune evasion proteins, M4 codes for a soluble glycopeptide acting as immunomodulator and/or immunostimulator.

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T-Cell Responses to the M3 Immune Evasion Protein of Murid Gammaherpesvirus 68 Are Partially Protective and Induced with Lytic Antigen Kinetics

Cited by 13 publications

References 32 publications

Cell-Mediated Immunity toToxoplasma gondiiDevelops Primarily by Local Th1 Host Immune Responses in the Absence of Parasite Replication

Cell-Mediated Immunity toToxoplasma gondiiDevelops Primarily by Local Th1 Host Immune Responses in the Absence of Parasite Replication

Induction of Protective Immunity against Murine Gammaherpesvirus 68 Infection in the Absence of Viral Latency

Comparison of pathogenic properties of the murid gammaherpesvirus (MuHV 4) strains: a role for immunomodulatory proteins encoded by the left (5′-)end of the genome

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