Complex Formation among Murine Cytomegalovirus US22 Proteins Encoded by Genes M139, M140, and M141

Karabekian, Zaruhi; Hanson, Laura K.; Slater, Jacquelyn S.; Krishna, Neel K.; Bolin, Lisa L.; Kerry, Julie A.; Campbell, Ann E.

doi:10.1128/jvi.79.6.3525-3535.2005

Cited by 12 publications

(23 citation statements)

References 26 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3A and B) (18). The use of anti-␣-tubulin antibodies in the current study revealed that this site is adjacent to the microtubule organizing center (MTOC).…”

Section: Vol 83 2009 Role Of M140 In MCMV Capsid Assembly In Macropmentioning

confidence: 99%

“…The M139, M140, and M141 early gene products form at least three stable complexes that colocalize to a perinuclear cis-Golgi region in infected macrophages (18). Sequence analysis of the three genes does not reveal any consensus functional domains, with the exception of a putative nuclear localization sequence within M139 and M141 (15).…”

Section: Macrophages Are An Important Target Cell For Infection With mentioning

confidence: 99%

“…In fact, when transiently expressed alone under the control of the HCMV major immediate-early promoter, pM140 is distributed diffusely throughout the nucleus (18). However, it relocalizes to a perinuclear cytoplasmic site when coexpressed with one of its binding partners, pM141 (18).…”

Section: Vol 83 2009 Role Of M140 In MCMV Capsid Assembly In Macropmentioning

confidence: 99%

“…Second, pM140 is a component of all three complexes identified: a pM140-pM141 complex and two pM139-pM140-pM141 complexes that differ in size and/or mass (18). Third, pM140 localizes to the nucleus but is redistributed to the cytoplasm when expressed with pM141 (18).…”

Section: Macrophages Are An Important Target Cell For Infection With mentioning

confidence: 99%

“…The plasmid expressing a fusion protein of M140 with green fluorescent protein (GFP) under the control of the M140 promoter was generated from pGFPM140 (18). First, a HindIII-BamHI fragment (MCMV bases 195847 to 194371) was cloned into pGFPM140 digested with HindIII and BamHI and designated pGFP140J.…”

Section: Cells and Virusesmentioning

confidence: 99%

See 4 more Smart Citations

Murine Cytomegalovirus Capsid Assembly Is Dependent on US22 Family Gene M140 in Infected Macrophages

Hanson

Slater

Cavanaugh

et al. 2009

J Virol

Self Cite

View full text Add to dashboard Cite

Macrophages are an important target cell for infection with cytomegalovirus (CMV).A number of viral genes that either are expressed specifically in this cell type or function to optimize CMV replication in this host cell have now been identified. Among these is the murine CMV (MCMV) US22 gene family member M140, a nonessential early gene whose deletion (RV⌬140) leads to significant impairment in virus replication in differentiated macrophages. We have now determined that the defect in replication is at the stage of viral DNA encapsidation. Although the rate of RV⌬140 genome replication and extent of DNA cleavage were comparable to those for revertant virus, deletion of M140 resulted in a significant reduction in the number of viral capsids in the nucleus, and the viral DNA remained sensitive to DNase treatment. These data are indicative of incomplete virion assembly. Steady-state levels of both the major capsid protein (M86) and tegument protein M25 were reduced in the absence of the M140 protein (pM140). This effect may be related to the localization of pM140 to an aggresome-like, microtubule organizing center-associated structure that is known to target misfolded and overexpressed proteins for degradation. It appears, therefore, that pM140 indirectly influences MCMV capsid formation in differentiated macrophages by regulating the stability of viral structural proteins.

show abstract

“…3A and B) (18). The use of anti-␣-tubulin antibodies in the current study revealed that this site is adjacent to the microtubule organizing center (MTOC).…”

Section: Vol 83 2009 Role Of M140 In MCMV Capsid Assembly In Macropmentioning

confidence: 99%

Section: Macrophages Are An Important Target Cell For Infection With mentioning

confidence: 99%

Section: Vol 83 2009 Role Of M140 In MCMV Capsid Assembly In Macropmentioning

confidence: 99%

Section: Macrophages Are An Important Target Cell For Infection With mentioning

confidence: 99%

Section: Cells and Virusesmentioning

confidence: 99%

See 3 more Smart Citations

Murine Cytomegalovirus Capsid Assembly Is Dependent on US22 Family Gene M140 in Infected Macrophages

Hanson

Slater

Cavanaugh

et al. 2009

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

Role of mutations identified in ORFs M27, M36, m139, m141, and m143 in the temperature‐sensitive phenotype of murine cytomegalovirus mutant tsm5

Al-Ali

Timoshenko

Martin

et al. 2012

Journal of Medical Virology

View full text Add to dashboard Cite

A mutant of murine cytomegalovirus (MCMV), tsm5, which is temperature‐sensitive for replication in murine embryo fibroblasts at 40°C, failed to replicate to detectable levels in mice. A total of 18 non‐synonymous mutations have been identified in tsm5. In a previous study, a mutation (C890Y) identified in the M70 primase gene, when introduced into the wt M70 primase, resulted in a mutant with reduced viral replication at 40°C in vitro and which was severely attenuated in vivo. Five other previously identified mutations may also contribute to the tsm5 phenotype: (1) an A658S mutation in a protein expressed by the M27 ORF; (2) a V54I mutation in M36; (3) a Y565* mutation in m139; (4) a V195M mutation in m141; and (5) an M232I mutation in m143. In the present study, the above‐mentioned mutations were introduced individually (M27, M36, m139, m141, m143) or together (M27/M36) into the MCMV K181 (Perth) variant bacterial artificial chromosome (BAC) using RecE/T homologous recombination. Growth in culture revealed that, apart from the double mutant (M27 and M36) and the m139 mutant, the introduced mutations in the above‐mentioned genes did not show a temperature‐sensitive phenotype in MEF or Raw 264.7 macrophage cells compared to their revertants or the wt virus. In contrast, replication of the M27/M36 double mutant was drastically reduced in MEFs at 40°C and in macrophages at 37°C. Replication of the m139 mutant was reduced in MEF cells at 40°C but not in macrophages. Thus, at least three further mutations contribute to the tsm5 phenotype. J. Med. Virol. 84:912–922, 2012. © 2012 Wiley Periodicals, Inc.

show abstract

Upregulation of CD94/NKG2A receptors and Qa-1b ligand during murine cytomegalovirus infection of salivary glands

Cavanaugh

Raulet

Campbell

2007

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

Following acute infection, murine cytomegalovirus (MCMV) replicates persistently in the salivary glands, despite the vigorous response of activated CD8 T cells that infiltrate this gland. Virus-specific CD8 T lymphocytes isolated from this organ were found to express the inhibitory CD94/NKG2A receptor that, in some virus models, confers an inhibitory response to cytotoxic T lymphocytes (CTLs). In response to MCMV infection, expression of the CD94/NKG2A ligand, Qa-1 b , increased dramatically in the submandibular gland (SMG) prior to upregulation of H-2D d . However, there was no net negative impact on virus-specific T-cell function, as virus titres were similar in CD94 " and CD94 + mice. CD94/NKG2A expression, also known to inhibit apoptosis, did not influence the numbers of accumulated T, NK and NK T cells. These data indicate that expression of inhibitory CD94/NKG2A receptors does not account for the failure of MCMV-specific CTLs to clear the SMG of infection.Cytomegaloviruses (CMVs) are ubiquitous betaherpesviruses that persist in their host for life following acute infection. In the immunocompetent host, this lifelong infection is typically asymptomatic; however, virus is excreted in mucosal secretions intermittently and for extended periods of time in the absence of clinical disease. Murine CMV (MCMV) infection within the salivary gland serves as a model for prolonged mucosal infection and shedding. In MCMV-infected mice, virus replicates to high titres in the salivary gland long after it is cleared from systemic organs, including the spleen, lung, liver, kidney, adrenal glands and lymph nodes (Jonjic et al., 1989). CD8 T cells are necessary and sufficient for clearing infectious virus from all target organs except the salivary gland (Jonjic et al., 1989;Pavic et al., 1993), where persistent virus replication is confined to the acinar epithelial cells (Jonjic et al., 1989). The eventual elimination of MCMV from acinar epithelial cells requires CD4 T cells (Jonjic et al., 1989), as well as the production of gamma interferon (IFN-c) and tumour necrosis factor alpha (Pavic et al., 1993).A previous study from our laboratory demonstrated a vigorous and sustained immune response to MCMV in the submaxillary (submandibular) gland (SMG) (Cavanaugh et al., 2003). At the peak of virus replication (14-21 days post-infection), infiltrating CD8 T cells predominated overwhelmingly. Notably, these CD8 T cells were highly functional, expressing IFN-c and readily lysing virusinfected target cells ex vivo. Compared with the robust number of CD8 T cells, other potential effector cells increased moderately (NK T), minimally (CD4 + T) or not at all (NK). It remains unclear how virus replication within the acinar epithelial cells resists the antiviral effects of the activated CD8 T cells. In support of the theory that infected SMG epithelial cells are relatively resistant to cytotoxic T-lymphocyte (CTL)-mediated lysis, the MCMV-encoded immunoevasion genes that inhibit CTL recognition of infected target cells (m04, m06 and m152) ...

show abstract

Complex Formation among Murine Cytomegalovirus US22 Proteins Encoded by Genes M139, M140, and M141

Cited by 12 publications

References 26 publications

Murine Cytomegalovirus Capsid Assembly Is Dependent on US22 Family Gene M140 in Infected Macrophages

Murine Cytomegalovirus Capsid Assembly Is Dependent on US22 Family Gene M140 in Infected Macrophages

Role of mutations identified in ORFs M27, M36, m139, m141, and m143 in the temperature‐sensitive phenotype of murine cytomegalovirus mutant tsm5

Upregulation of CD94/NKG2A receptors and Qa-1b ligand during murine cytomegalovirus infection of salivary glands

Contact Info

Product

Resources

About