Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus.
Lichen planus (LP) is a common inflammatory skin disease of unknown etiology. Reports of a common transactivation of quiescent human endogenous retroviruses (HERVs) support the connection of viruses to the disease. HERVs are ancient retroviral sequences in the human genome and their transcription is often deregulated in cancer and autoimmune diseases. We explored the transcriptional activity of HERV sequences as well as the antiviral restriction factor and interferon-inducible genes in the skin from LP patients and healthy control (HC) donors. The study included 13 skin biopsies from patients with LP and 12 controls. Real-time PCR assay identified significant decrease in the HERV-K gag and env mRNA expression levels in LP subjects, when compared to control group. The expressions of HERV-K18 and HERV-W env were also inhibited in the skin of LP patients. We observed a strong correlation between HERV-K gag with other HERV sequences, regardless the down-modulation of transcripts levels in LP group. In contrast, a significant up-regulation of the cytidine deaminase APOBEC 3G (apolipoprotein B mRNA-editing), and the GTPase MxA (Myxovirus resistance A) mRNA expression level was identified in the LP skin specimens. Other transcript expressions, such as the master regulator of type I interferon-dependent immune responses, STING (stimulator of interferon genes) and IRF-7 (interferon regulatory factor 7), IFN-β and the inflammassome NALP3, had increased levels in LP, when compared to HC group. Our study suggests that interferon-inducible factors, in addition to their role in innate immunity against exogenous pathogens, contribute to the immune control of HERVs. Evaluation of the balance between HERV and interferon-inducible factor expression could possibly contribute to surveillance of inflammatory/malignant status of skin diseases.
Dermatological Outpatient Clinic, Hospital das Clínicas, Medical School of the University of São Paulo, São Paulo, Brazil.
Marcelle Almeida de Sousa
MA
Nogueira
Camila Fátima Biancardi
CF
Gavioli
Nátalli Zanete
NZ
Pereira
Gabriel Costa
GC
de Carvalho
Rosana
R
Domingues
Valéria
V
Aoki
Maria Notomi
MN
Sato
D000071480:APOBEC-3G Deaminase; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015967:Gene Expression Regulation, Viral; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007157:Immunologic Surveillance; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008010:Lichen Planus / Q000235:genetics / Q000276:immunology* / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000821:virology; D018089:Superantigens / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D055815:Young Adult; D000099197:STING Protein
D000071480:APOBEC-3G Deaminase; D002352:Carrier Proteins; D003564:Cytidine Deaminase; D015686:Gene Products, env; D015683:Gene Products, gag; D050839:Interferon Regulatory Factor-7; D016899:Interferon-beta; D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011257:Pregnancy Proteins; D018089:Superantigens; C107453:ERVK-18 protein, human; C579071:MX1 protein, human; C453881:NLRP3 protein, human; C532857:STING1 protein, human; D000099197:STING Protein; C405335:syncytin; C464924:APOBEC3G protein, human