Adenovirus infection induces loss of HLA class I and CD3 antigens, but does not induce cell surface presentation of the La (SS-B) autoantigen

Peek, Ron; Westphal, Johan R.; Pruijn, Ger J. M.; Kemp, Anthony J.; Venrooij, Walther J. van

doi:10.1111/j.1365-2249.1994.tb06041.x

Cited by 6 publications

(4 citation statements)

References 31 publications

(21 reference statements)

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“…The nuclear localization is not restricted to the nucleoplasm, since La has been found in the nucleolus as well (45). In contrast to the nuclear immunofluorescence, cytoplasmic staining by anti-La antibodies has been reported under certain stress conditions, such as viral infection (19,(46)(47)(48)(49), UV irradiation (50)(51)(52), and inhibition of mRNA synthesis (53). Based on these observations, La was proposed to shuttle between the nucleus and cytoplasm and to be involved in nucleocytoplasmic transport of RNA polymerase III transcripts (54).…”

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confidence: 99%

Detailed Analysis of the Phosphorylation of the Human La (SS-B) Autoantigen. (De)phosphorylation Does Not Affect Its Subcellular Distribution

et al. 2000

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The La (SS-B) autoantigen is an evolutionarily conserved phosphoprotein which plays an important role, most likely as an RNA chaperone, in various processes, such as the biosynthesis and maturation of RNA polymerase III transcripts in the cell nucleus and (internal) initiation of translation in the cytoplasm. In this study, the phosphorylation state of this protein from human HeLa and HEp-2 cells was characterized by high-resolution two-dimensional IEF/SDS-PAGE analysis, and phosphorylation sites were mapped by nanoelectrospray mass spectrometry. Furthermore, the effect of phosphorylation at the sites identified on the subcellular distribution of the protein was studied by site-directed mutagenesis. At least 14 isoelectric isoforms were discerned on 2-D gels with La protein from both types of cells. Metabolic labeling in combination with alkaline phosphatase treatment revealed that only a limited number of these isoforms could be attributed to phosphorylation. Four phosphorylation sites, Thr-302, Ser-325, Thr-362, and Ser-366, were mapped by mass spectrometric analysis of the isolated La protein from HeLa cells or the carboxy-terminal half of this protein. The analysis of mutants of La, in which the respective phosphorylated residues were replaced by either a neutral (alanine) or an acidic (aspartate) residue, by microinjection into Xenopus laevis oocytes on the one hand and transfection of HEp-2 cells on the other hand revealed that the subcellular distribution of this protein was not affected by these amino acid substitutions. These results strongly suggest that the signals that determine the subcellular distribution of this protein are not regulated by (de)phosphorylation of the target residues examined.

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confidence: 99%

Detailed Analysis of the Phosphorylation of the Human La (SS-B) Autoantigen. (De)phosphorylation Does Not Affect Its Subcellular Distribution

et al. 2000

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“…A study has shown that adenovirus E3-19k inhibits the phosphorylation of major histocompatibility complex (MHC) class I proteins in the rough endoplasmic reticulum (RER) with ability to bind to HLA molecules, during the infection of a human cell line ( Lippe et al, 1991 ). E3-19K proteins with MHC (class I and class II-restricted) activity binds with high affinity to HLA-A and HLA-B molecules, and counteract activation of CD8 + and CD4 + T cells ( Scheppler et al, 1989 ; Peek et al, 1994 ; Li et al, 2016 ). Thus, vaccines will be unsuitable due to declining of CD4 + T cell counts, but antiviral therapies are a promising therapeutic strategy against HAdV infection ( Widman et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Reduction in the level of surface-expressed HLA class I cause Immunosuppression and it has been reported to occur during infection by several viruses including HAdV through mechanism that differs from inhibition of host cell protein synthesis. This is possible by downregulation of the surface expression of the T cell specific CD3 complex and HLA class I, which resulted in impairment of the presentation of viral peptides to the immune system and thus prevent the initiation of cell-mediated immunity to the virus ( Boshkov et al, 1992 ; Peek et al, 1994 ).…”

Section: Discussionmentioning

confidence: 99%

“…Computational approaches such as in silico molecular docking and molecular dynamic simulation, provide opportunities for target discovery and drug repositioning are useful in modern pharmaceutical processes. Drug repurposing or repositioning is now a significantly relevant strategy to circumvent the roadblocks in novel drug discovery (Pushpakom et al, 2019;Dodge et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

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Human adenovirus DNA polymerase is evolutionarily and functionally associated with human telomerase reverse transcriptase based on in silico molecular characterization that implicate abacavir and zidovudine

Fatoki¹

2023

Front. Bioinform.

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Human adenoviruses (HAdVs) are non-enveloped, small double stranded DNA (dsDNA) viruses that cause asymptomatic infections, clinical syndromes and significant susceptibility to infections in immunocompromised people. The aim of the present study was to identify critical host proteins and HAdV hypothetical proteins that could be developed as potential host-viral targets for antiHAdV therapy. Here, the function of selected hypothetical proteins of HAdV based on phylogenetic relationship with the therapeutic targets of antiretroviral drugs of human immunodeficiency virus (HIV) was predicted computationally, and characterized the molecular dynamics and binding affinity of DNA polymerase of HAdV. Thirty-eight hypothetical proteins (HPs) of human adenovirus (HAdV) were used in this study. The results showed that HAdV DNA polymerase (P03261) is related to Human TERT (O14746) and HLA-B (P01889) genes. The protein-protein interaction of human five molecular targets (PNP, TERT, CCR5, HLA-B, and NR1I2) of ARVDs are well-coordinated/networked with CD4, AHR, FKBP4, NR3C1, HSP90AA1, and STUB1 proteins in the anti-HIV infection mechanism. The results showed that the free energy score of abacavir and zidovudine binding to HAdV DNA polymerase are −5.8 and −5.4 kcal mol-1 respectively. Also, the control drug, cidofovir and ganciclovir have less binding affinity for DNA polymerase of HAdV when compare to that of abacavir and zidovudine. Similarity was observed in the binding of abacavir and zidovudine to HAdV DNA polymerase (ASP742, ALA743, LEU772, ARG773 and VAL776). In conclusion, combination of abacavir and zidovudine was predicted to be potential therapy for controlling HAdV infection targeting HAdV DNA polymerase.

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Aberrant expression pattern of the SS‐B/La antigen in the labial salivary glands of patients with Sjögren's syndrome

Wilde¹,

Kater²,

Bodeutsch³

et al. 1996

Arthritis & Rheumatism

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Objective. Salivary glands of patients with Sjögren's syndrome (SS) have been shown to be a site of anti‐SS‐B/La antibody production. The present study investigated differences in the localization of the SS‐B/La antigen in labial salivary gland (LSG) tissue between SS and non‐SS patients, which may explain the local antigen‐driven anti–SS‐B/La response. Methods. Distribution of SS‐B/La was studied immunohistologically in the LSG biopsy samples of 9 SS patients, 10 non‐SS patients, and in normal tissues obtained at autopsy within 2 hours after death, using a mouse monoclonal antibody directed to SS‐B/La. In 3 SS and 3 non‐SS patients, LSGs were also studied with affinity‐purified biotinylated human antibodies directed against SS‐B/La. Results. In the non‐SS patients, SS‐B/La was primarily observed in the nucleoli of acinic cells of the LSGs. Patients with either primary SS or secondary SS showed an accumulation of SS‐B/La in the nucleoplasm of acinic cells. In the SS patients, SS‐B/La was also detected in the cytoplasm as a diffuse or perinuclear staining. Sometimes, SS‐B/La was found along the membrane of acinic cells as well. This aberrant nuclear and cytoplasmic distribution of SS‐B/La in SS patients correlated well with abnormalities in the composition of the plasma cell population in the LSGs, but not with a lymphocytic focus score > 1. Conclusion. The accumulation and redistribution of SS‐B/La in the LSGs may play an important role in the local antigen‐driven anti–SS‐B/La response in SS, and can also be used to improve the diagnostic possibilities of the LSG biopsy.

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Adenovirus infection induces loss of HLA class I and CD3 antigens, but does not induce cell surface presentation of the La (SS-B) autoantigen

Cited by 6 publications

References 31 publications

Detailed Analysis of the Phosphorylation of the Human La (SS-B) Autoantigen. (De)phosphorylation Does Not Affect Its Subcellular Distribution

Detailed Analysis of the Phosphorylation of the Human La (SS-B) Autoantigen. (De)phosphorylation Does Not Affect Its Subcellular Distribution

Human adenovirus DNA polymerase is evolutionarily and functionally associated with human telomerase reverse transcriptase based on in silico molecular characterization that implicate abacavir and zidovudine

Aberrant expression pattern of the SS‐B/La antigen in the labial salivary glands of patients with Sjögren's syndrome

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