scholarly journals Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68.

1996 ◽  
Vol 70 (10) ◽  
pp. 6775-6780 ◽  
Author(s):  
K E Weck ◽  
M L Barkon ◽  
L I Yoo ◽  
S H Speck ◽  
I V Virgin HW
Keyword(s):  
B Cells ◽  
Murine Gammaherpesvirus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

scholarly journals Dendritic Cells Loaded with Tumor B Cells Elicit Broad Immunity against Murine Gammaherpesvirus 68 but Fail To Prevent Long-Term Latency

2010 ◽  
Vol 84 (17) ◽  
pp. 8975-8979
Author(s):  
Janet Weslow-Schmidt ◽  
Fang Ye ◽  
Stephanie S. Cush ◽  
Kathleen A. Stuller ◽  
Marcia A. Blackman ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Acute Infection ◽  
Dendritic Cell Vaccination ◽  
Murine Gammaherpesvirus ◽  
Attenuated Viruses ◽  
Gammaherpesvirus 68 ◽  
Vaccine Approach ◽  
Murine Gammaherpesvirus 68

ABSTRACT It is still unknown whether a noninfectious gammaherpesvirus vaccine is able to prevent or reduce virus persistence. This led us to use dendritic cells loaded with tumor B cells as a vaccine approach for the murine gammaherpesvirus 68 (γHV68) model of infection. Dendritic cells loaded with UV-irradiated latently infected tumor B cells induce broad, strong, and long-lasting immunity against γHV68. Dendritic cell vaccination prevents the enlargement of lymph nodes and severely limits acute infection and early latency but does not prevent γHV68 from establishing long-term latency. Our findings support the concept that attenuated viruses may be the best vaccine option for preventing gammaherpesvirus persistence.

scholarly journals Evidence for a Multiprotein Gamma-2 Herpesvirus Entry Complex

2007 ◽  
Vol 81 (23) ◽  
pp. 13082-13091 ◽  
Author(s):  
Laurent Gillet ◽  
Philip G. Stevenson
Keyword(s):  
B Cells ◽  
Specific Antibody ◽  
Cell Binding ◽  
Murine Gammaherpesvirus ◽  
Single Entry ◽  
Single Complex ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68 ◽  
Better Than

ABSTRACT Herpesviruses use multiple virion glycoproteins to enter cells. How these work together is not well understood: some may act separately or they may form a single complex. Murine gammaherpesvirus 68 (MHV-68) gB, gH, gL, and gp150 all participate in entry. gB and gL are involved in binding, gB and gH are conserved fusion proteins, and gp150 inhibits cell binding until glycosaminoglycans are engaged. Here we show that a gH-specific antibody coprecipitates gB and thus that gH and gB are associated in the virion membrane. A gH/gL-specific antibody also coprecipitated gB, implying a tripartite complex of gL/gH/gB, although the gH/gB association did not require gL. The association was also independent of gp150, and gp150 was not demonstrably bound to gB or gH. However, gp150 incorporation into virions was partly gL dependent, suggesting that it too contributes to a single entry complex. gp150− and gL− gp150− mutants bound better than the wild type to B cells and readily colonized B cells in vivo. Thus, gp150 and gL appear to be epithelial cell-adapted accessories of a core gB/gH entry complex. The cell binding revealed by gp150 disruption did not require gL and therefore seemed most likely to involve gB.

scholarly journals De Novo Infection of B Cells during Murine Gammaherpesvirus 68 Latency

2011 ◽  
Vol 85 (20) ◽  
pp. 10920-10925 ◽  
Author(s):  
M. L. Freeman ◽  
C. E. Burkum ◽  
E. J. Yager ◽  
D. L. Woodland ◽  
M. A. Blackman
Keyword(s):  
B Cells ◽  
De Novo ◽  
Murine Gammaherpesvirus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

scholarly journals The Absence of M1 Leads to Increased Establishment of Murine Gammaherpesvirus 68 Latency in IgD-Negative B Cells

2013 ◽  
Vol 87 (6) ◽  
pp. 3597-3604 ◽  
Author(s):  
L. T. Krug ◽  
A. G. Evans ◽  
L. M. Gargano ◽  
C. R. Paden ◽  
S. H. Speck
Keyword(s):  
B Cells ◽  
Murine Gammaherpesvirus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

scholarly journals Identification of Infected B-Cell Populations by Using a Recombinant Murine Gammaherpesvirus 68 Expressing a Fluorescent Protein

2009 ◽  
Vol 83 (13) ◽  
pp. 6484-6493 ◽  
Author(s):  
Christopher M. Collins ◽  
Jeremy M. Boss ◽  
Samuel H. Speck
Keyword(s):  
B Cells ◽  
Virus Infection ◽  
Plasma Cells ◽  
Fluorescent Protein ◽  
Viral Latency ◽  
Murine Gammaherpesvirus ◽  
Latently Infected ◽  
Infected Cells ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT Infection of inbred mice with murine gammaherpesvirus 68 (MHV68) has proven to be a powerful tool to study gammaherpesvirus pathogenesis. However, one of the limitations of this system has been the inability to directly detect infected cells harvested from infected animals. To address this issue, we generated a transgenic virus that expresses the enhanced yellow fluorescent protein (YFP), driven by the human cytomegalovirus immediate-early promoter and enhancer, from a neutral locus within the viral genome. This virus, MHV68-YFP, replicated and established latency as efficiently as did the wild-type virus. During the early phase of viral latency, MHV68-YFP efficiently marked latently infected cells in the spleen after intranasal inoculation. Staining splenocytes for expression of various surface markers demonstrated the presence of MHV68 in distinct populations of splenic B cells harboring MHV68. Notably, these analyses also revealed that markers used to discriminate between newly formed, follicular and marginal zone B cells may not be reliable for phenotyping B cells harboring MHV68 since virus infection appears to modulate cell surface expression levels of CD21 and CD23. However, as expected, we observed that the overwhelming majority of latently infected B cells at the peak of latency exhibited a germinal center phenotype. These analyses also demonstrated that a significant percentage of MHV68-infected splenocytes at the peak of viral latency are plasma cells (ca. 15% at day 14 and ca. 8% at day 18). Notably, the frequency of virus-infected plasma cells correlated well with the frequency of splenocytes that spontaneously reactivate virus upon explant. Finally, we observed that the efficiency of marking latently infected B cells with the MHV68-YFP recombinant virus declined at later times postinfection, likely due to shut down of transgene expression, and indicating that the utility of this marking strategy is currently limited to the early stages of virus infection.

scholarly journals Selective Gene Expression of Latent Murine Gammaherpesvirus 68 in B Lymphocytes

2003 ◽  
Vol 77 (13) ◽  
pp. 7308-7318 ◽  
Author(s):  
Sofia Marques ◽  
Stacey Efstathiou ◽  
K. G. Smith ◽  
Matthias Haury ◽  
J. Pedro Simas
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Critical Role ◽  
Murine Gammaherpesvirus ◽  
Virus Transcription ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68 ◽  
Germinal Center B Cells

ABSTRACT Intranasal infection of mice with murine gammaherpesvirus 68 (MHV-68), a virus genetically related to the human pathogen Kaposi's sarcoma-associated herpesvirus, results in a persistent, latent infection in the spleen and other lymphoid organs. Here, we have determined the frequency of virus infection in splenic dendritic cells, macrophages, and several B-cell subpopulations, and we quantified cell type-dependent virus transcription patterns. The frequencies of virus genome positive cells were maximal at 14 days postinfection in all splenic cell populations analyzed. Marginal zone and germinal center B cells harbored the highest frequency of infection and the former population accounted for approximately half the total number of infected B cells. Analysis of virus transcription during the establishment of latency revealed that virus gene expression in B cells was restricted and dependent on the differentiation stage of the B cell. Notably, transcription of ORF73 was detected in germinal center B cells, a finding in agreement with the predicted latent genome maintenance function of ORF73 in dividing cells. At late times after infection, virus DNA could only be detected in newly formed and germinal center B cells, which suggests that B cells play a critical role in facilitating life-long latency.

scholarly journals Age-associated B cells are critical for the control of latent gammaherpesvirus 68 infection

2021 ◽  
Author(s):  
Isobel C. Mouat ◽  
Iryna Shanina ◽  
Marc S. Horwitz
Keyword(s):  
B Cells ◽  
Viral Infections ◽  
Acute Infection ◽  
Effective Control ◽  
Murine Gammaherpesvirus ◽  
Barr Virus ◽  
Gamma Herpesvirus ◽  
Epstein Barr ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

Age-associated B cells (ABCs; CD19+CD11c+T-bet+) are increased during an array of viral infections, though their role during viral latency is unexplored. Here, we use murine gammaherpesvirus 68 (γHV68), a homolog of Epstein-Barr virus that latently infects B cells, to demonstrate that ABCs are necessary for the effective control of gamma-herpesvirus latency. We observe that ABCs expand in the spleen during acute infection and persist at least 150 days post-infection. During acute and latent infection ABCs secrete IFNγ and TNF. Using a strain of γHV68 that is cleared following acute infection, we show that ABCs persist in the absence of latent virus, though they secrete less IFNγ and TNF. With a fluorescent virus we demonstrate that ABCs are infected with γHV68 at similar rates to other mature B cells. We find that mice without ABCs display defects in anti-viral IgG2a/c antibodies and are less able to maintain γHV68 latency when challenged with heterologous infection. Together, these results indicate that ABCs are a persistent subset during latent viral infection that controls γHV68 reactivation from latency.

scholarly journals NF-κB p50 Plays Distinct Roles in the Establishment and Control of Murine Gammaherpesvirus 68 Latency

2009 ◽  
Vol 83 (10) ◽  
pp. 4732-4748 ◽  
Author(s):  
Laurie T. Krug ◽  
Christopher M. Collins ◽  
Lisa M. Gargano ◽  
Samuel H. Speck
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Virus Replication ◽  
Direct Analysis ◽  
Virus Reactivation ◽  
Chimeric Mice ◽  
Murine Gammaherpesvirus ◽  
Persistent Virus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT NF-κB signaling is critical to the survival and transformation of cells infected by the human gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. Here we have examined how elimination of the NF-κB transcription factor p50 from mice affects the life cycle of murine gammaherpesvirus 68 (MHV68). Notably, mice lacking p50 in every cell type were unable to establish a sufficiently robust immune response to control MHV68 infection, leading to high levels of latently infected B cells detected in the spleen and persistent virus replication in the lungs. The latter correlated with very low levels of virus-specific immunoglobulin G (IgG) in the infected p50−/− mice at day 48 postinfection. Because the confounding impact of the loss of p50 on the host response to MHV68 infection prevented a direct analysis of the role of this NF-κB family member on MHV68 latency in B cells, we generated and infected mixed p50+/+/p50−/− bone marrow chimeric mice. We show that the chimeric mice were able to control acute virus replication and exhibited normal levels of virus-specific IgG at 3 months postinfection, indicating the induction of a normal host immune response to MHV68 infection. However, in p50+/+/p50−/− chimeric mice the p50−/− B cells exhibited a significant defect compared to p50+/+ B cells in supporting MHV68 latency. In addition to identifying a role for p50 in the establishment of latency, we determined that the absence of p50 in a subset of the hematopoietic compartment led to persistent virus replication in the lungs of the chimeric mice, providing evidence that p50 is required for controlling virus reactivation. Taken together, these data demonstrate that p50 is required for immune control by the host and has distinct tissue-dependent roles in the regulation of murine gammaherpesvirus latency during chronic infection.

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