Fragment of tegument protein pp65 of human cytomegalovirus induces autoantibodies in BALB/c mice

Hsieh, Ao-Ho; Jhou, Yi-Jyun; Liang, Chung-Ting; Chang, Mei‐Chi; Wang, Shih-Lien

doi:10.1186/ar3481

Cited by 33 publications

(45 citation statements)

References 33 publications

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“…Compared with normal controls, the presence of HCMV DNA and the HCMV genome copy number was significantly higher in SLE patients [9]. Additionally, most SLE patients harbor specific antibodies to the HCMV PP65 Cterminal [10], and the U1 small nuclear ribonucleoprotein (U1 snRNP) antibody, which is highly relevant to autoimmune disease, is more common in patients with SLE and animals infected by HCMV or in immunized animals [11,12]. However, the studies of James et al suggested that HCMV infection was not related to SLE [4].…”

Section: Discussionmentioning

confidence: 94%

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods

et al. 2015

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Human cytomegalovirus (HCMV), a β-herpes virus subfamily member, leads to a lifelong, latent infection in most humans, but the correlation between HCMV infection and systemic lupus erythematosus (SLE) remains controversial. We analyzed the relevance of HCMV infection in SLE by analyzing the peripheral blood leukocytes (PBLs) and serum samples of 60 patients with SLE and 111 healthy individuals. HCMV genes UL55 and UL138 were detected in PBLs by polymerase chain reaction (PCR), and HCMV-specific serum IgG and IgM antibodies were investigated by enzyme-linked immunosorbent assay. The relationship between cellular HCMV infection in PBLs and common clinical indicators of SLE was further explored. Data indicated that the frequency of positive IgG and IgM anti-CMV antibodies was not significantly different in SLE patients and controls. However, compared to the healthy controls, the titers of IgG and IgM anti-CMV antibodies in SLE patients were significantly higher. The detection of cellular HCMV infection showed that almost all subjects were positive for UL138 gene in PBLs, but the positivity for UL55 gene was lower in PBLs. HCMV UL138 detection in PBLs was highly consistent with the frequency of the HCMV-specific IgG test and did not show significant difference in SLE patients and healthy controls. However, compared with that in healthy people, the positivity rate for cellular HCMV UL55 detection was significantly higher in SLE patients (P < 0.001). In addition, cellular HCMV UL55 with positive detection in PBLs was associated with significantly different clinical characteristics of SLE than that with negative detection. In conclusion, our data confirmed that the HCMV infection was related to the development of SLE. Especially, some clinical strains or substrains of HCMV, such as containing the UL55 gene in HCMV's genome, might play a vital role in the development of SLE.

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Section: Discussionmentioning

confidence: 94%

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods

et al. 2015

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“…Immune reactivity against this peptide was also found in 14–20% of patients with rheumatoid arthritis, Sjögren syndrome and systemic sclerosis but only in 4% of healthy controls 121 . Antibodies against HCMV pp65 cross-reacted with nuclear proteins and double-stranded DNA and were therefore proposed to be pathogenic 121 . This hypothesis is further supported by animal experiments; in lupus-prone mice, immunization with pp65 resulted in autoantibody production and glomerulonephritis 122 .…”

Section: Impact Of Hcmv In Dcs On Clinical Pathologymentioning

confidence: 94%

“…Patients with HCMV-induced autoimmunity may be coinfected by other pathogens, 120 which may increase TLR activation and complement activation, resulting in an enhanced immune response. Recently, it was reported that a majority of SLE patients have antibodies to the C terminus of the HCMV protein pp65, in particular to a subfragment of pp65 121 . Immune reactivity against this peptide was also found in 14–20% of patients with rheumatoid arthritis, Sjögren syndrome and systemic sclerosis but only in 4% of healthy controls 121 .…”

Section: Impact Of Hcmv In Dcs On Clinical Pathologymentioning

confidence: 99%

“…Recently, it was reported that a majority of SLE patients have antibodies to the C terminus of the HCMV protein pp65, in particular to a subfragment of pp65 121 . Immune reactivity against this peptide was also found in 14–20% of patients with rheumatoid arthritis, Sjögren syndrome and systemic sclerosis but only in 4% of healthy controls 121 . Antibodies against HCMV pp65 cross-reacted with nuclear proteins and double-stranded DNA and were therefore proposed to be pathogenic 121 .…”

Section: Impact Of Hcmv In Dcs On Clinical Pathologymentioning

confidence: 99%

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Dendritic cell biology in human cytomegalovirus infection and the clinical consequences for host immunity and pathology

Gredmark‐Russ

Söderberg‐Nauclér

2012

Virulence

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Human cytomegalovirus (HCMV), a member of the herpesvirus family, establishes life-long persistence and latency after primary infection and can be reactivated later in life. In immunosuppressed patients, it is an important pathogen that can cause severe disease. HCMV is also thought to play a causative role in inflammatory diseases and cancer. The virus can infect different immune cells, including dendritic cells (DCs) and can take advantage of host immune functions to avoid immune recognition. These characteristics have sparked major interest in understanding HCMV and its interaction with immune cells and their relevance to disease pathogenesis. In this review, we focus on the complex host-pathogen relationship between HCMV and DCs, including the persistence of the virus in these cells, their function in the immune response to HCMV infection and the potential clinical consequences of HCMV infection in DCs.

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“…Antibody preparation was performed as previously described [22]. In brief, moderated cyanogen bromide (CnBr) powder (Sigma Aldrich) was activated following the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice

Wang

et al. 2017

Arthritis Res Ther

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BackgroundHCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope.MethodsThe target epitope pp65422-439 reactivity and B cell epitope mapping was examined in serum from pp65422-439-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis.ResultsAnti-pp65422-439 antibody in serum either from patients with SLE or from pp65422-439-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65422-439-immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65422-439-derived decapeptides, one dominant epitope, pp65428-437, was identified in serum from pp65422-439-immunized mice and patients with SLE with anti-pp65422-439 antibody. Epitope spreading from pp65428-437 to pp65430-439 was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434 and pp65430-439. However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65430-439-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65428-437. ConclusionsOur data suggest that pp65428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1268-2) contains supplementary material, which is available to authorized users.

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Fragment of tegument protein pp65 of human cytomegalovirus induces autoantibodies in BALB/c mice

Cited by 33 publications

References 33 publications

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods

Dendritic cell biology in human cytomegalovirus infection and the clinical consequences for host immunity and pathology

B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice

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