A cumulative effect of risk allele number (<i>C8orf13–BLK</i> rs13277113A and <i>STAT4</i> rs7574865T) on susceptibility to polymyositis, dermatomyositis, and polymyositis/dermatomyositis.

<p>OR: Odds ratio, CI: confidence interval, PM: polymyositis, DM: dermatomyositis, N.S.: not significant.</p

Association between <i>C8orf13–BLK</i> rs13277113 and polymyositis/dermatomyositis.

<p>OR: Odds ratio, CI: confidence interval, PM: polymyositis, DM: dermatomyositis, N.S.: not significant.</p

Schematic diagram of the genome structures of wild type YK304 and the relevant domains of the recombinant viruses used in this study.

<p>Line 1, YK304 genome carrying a bacmid (BAC) in the intergenic region between UL3 and UL4. Line 2, domains encoding the UL40 to UL42 open reading frames. Line 3, UL41 gene encoding vhs. Lines 4-7, recombinant viruses with mutations in the UL41 gene. Line 8, domains encoding the Us11 to Us12 open reading frames and the viral replication origin S (Ori-S). Line 9, recombinant virus with mutation in the Us12 gene encoding ICP47.</p

MOESM1 of Six-helix bundle completion in the distal C-terminal heptad repeat region of gp41 is required for efficient human immunodeficiency virus type 1 infection

Additional file 1: Fig. S1. Interaction of the C34 (647+A) peptide with N36. A. CD spectrographic analysis of the complexes formed between N36 and C34 or its mutant C34 (647+A). Left panel, the secondary structure of complexes formed by C34 and N36 (dark blue) or C34 (647+A) and N36 (orange). Right panel, the stability of complexes formed by C34 with N36 (dark gray) and its mutants (light gray), as measured by thermal denaturation analysis

Image_3_Interferon regulatory factor 3 mediates effective antiviral responses to human coronavirus 229E and OC43 infection.tif

Interferon regulatory factors (IRFs) are key elements of antiviral innate responses that regulate the transcription of interferons (IFNs) and IFN-stimulated genes (ISGs). While the sensitivity of human coronaviruses to IFNs has been characterized, antiviral roles of IRFs during human coronavirus infection are not fully understood. Type I or II IFN treatment protected MRC5 cells from human coronavirus 229E infection, but not OC43. Cells infected with 229E or OC43 upregulated ISGs, indicating that antiviral transcription is not suppressed. Antiviral IRFs, IRF1, IRF3 and IRF7, were activated in cells infected with 229E, OC43 or severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). RNAi knockdown and overexpression of IRFs demonstrated that IRF1 and IRF3 have antiviral properties against OC43, while IRF3 and IRF7 are effective in restricting 229E infection. IRF3 activation effectively promotes transcription of antiviral genes during OC43 or 229E infection. Our study suggests that IRFs may be effective antiviral regulators against human coronavirus infection.</p

Image_4_Interferon regulatory factor 3 mediates effective antiviral responses to human coronavirus 229E and OC43 infection.tif

Interferon regulatory factors (IRFs) are key elements of antiviral innate responses that regulate the transcription of interferons (IFNs) and IFN-stimulated genes (ISGs). While the sensitivity of human coronaviruses to IFNs has been characterized, antiviral roles of IRFs during human coronavirus infection are not fully understood. Type I or II IFN treatment protected MRC5 cells from human coronavirus 229E infection, but not OC43. Cells infected with 229E or OC43 upregulated ISGs, indicating that antiviral transcription is not suppressed. Antiviral IRFs, IRF1, IRF3 and IRF7, were activated in cells infected with 229E, OC43 or severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). RNAi knockdown and overexpression of IRFs demonstrated that IRF1 and IRF3 have antiviral properties against OC43, while IRF3 and IRF7 are effective in restricting 229E infection. IRF3 activation effectively promotes transcription of antiviral genes during OC43 or 229E infection. Our study suggests that IRFs may be effective antiviral regulators against human coronavirus infection.</p

Image_2_Interferon regulatory factor 3 mediates effective antiviral responses to human coronavirus 229E and OC43 infection.tif

Interferon regulatory factors (IRFs) are key elements of antiviral innate responses that regulate the transcription of interferons (IFNs) and IFN-stimulated genes (ISGs). While the sensitivity of human coronaviruses to IFNs has been characterized, antiviral roles of IRFs during human coronavirus infection are not fully understood. Type I or II IFN treatment protected MRC5 cells from human coronavirus 229E infection, but not OC43. Cells infected with 229E or OC43 upregulated ISGs, indicating that antiviral transcription is not suppressed. Antiviral IRFs, IRF1, IRF3 and IRF7, were activated in cells infected with 229E, OC43 or severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). RNAi knockdown and overexpression of IRFs demonstrated that IRF1 and IRF3 have antiviral properties against OC43, while IRF3 and IRF7 are effective in restricting 229E infection. IRF3 activation effectively promotes transcription of antiviral genes during OC43 or 229E infection. Our study suggests that IRFs may be effective antiviral regulators against human coronavirus infection.</p

Table_1_Interferon regulatory factor 3 mediates effective antiviral responses to human coronavirus 229E and OC43 infection.pdf

Interferon regulatory factors (IRFs) are key elements of antiviral innate responses that regulate the transcription of interferons (IFNs) and IFN-stimulated genes (ISGs). While the sensitivity of human coronaviruses to IFNs has been characterized, antiviral roles of IRFs during human coronavirus infection are not fully understood. Type I or II IFN treatment protected MRC5 cells from human coronavirus 229E infection, but not OC43. Cells infected with 229E or OC43 upregulated ISGs, indicating that antiviral transcription is not suppressed. Antiviral IRFs, IRF1, IRF3 and IRF7, were activated in cells infected with 229E, OC43 or severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). RNAi knockdown and overexpression of IRFs demonstrated that IRF1 and IRF3 have antiviral properties against OC43, while IRF3 and IRF7 are effective in restricting 229E infection. IRF3 activation effectively promotes transcription of antiviral genes during OC43 or 229E infection. Our study suggests that IRFs may be effective antiviral regulators against human coronavirus infection.</p

Effect of depletion of CD8⁺ T cells or NK cells on YK511 (Us3K220M) replication in vivo.

<p>Six 6-week-old female C57BL/6J mice were mock-depleted or depleted of CD8⁺ T cells (A) or NK1.1⁺ cells (B) and infected with 1 x 10⁶ PFU YK511 (Us3-K220M) or YK513 (Us3-repair)/footpad. At 1 and 4 d post-infection, virus titers in the footpads from the infected mice were determined by standard plaque assays on Vero cells. Each data point is the mean ± standard error of the PFU/gram/footpad.</p

Us3 Kinase Encoded by Herpes Simplex Virus 1 Mediates Downregulation of Cell Surface Major Histocompatibility Complex Class I and Evasion of CD8⁺ T Cells

<div><p>Detection and elimination of virus-infected cells by CD8⁺ cytotoxic T lymphocytes (CTLs) depends on recognition of virus-derived peptides presented by major histocompatibility complex class I (MHC-I) molecules on the surface of infected cells. In the present study, we showed that inactivation of the activity of viral kinase Us3 encoded by herpes simplex virus 1 (HSV-1), the etiologic agent of several human diseases and a member of the <i>alphaherpesvirinae</i>, significantly increased cell surface expression of MHC-I, thereby augmenting CTL recognition of infected cells in vitro. Overexpression of Us3 by itself had no effect on cell surface expression of MHC-I and Us3 was not able to phosphorylate MHC-I in vitro, suggesting that Us3 indirectly downregulated cell surface expression of MHC-I in infected cells. We also showed that inactivation of Us3 kinase activity induced significantly more HSV-1-specific CD8⁺ T cells in mice. Interestingly, depletion of CD8⁺ T cells in mice significantly increased replication of a recombinant virus encoding a kinase-dead mutant of Us3, but had no effect on replication of a recombinant virus in which the kinase-dead mutation was repaired. These results indicated that Us3 kinase activity is required for efficient downregulation of cell surface expression of MHC-I and mediates evasion of HSV-1-specific CD8⁺ T cells. Our results also raised the possibility that evasion of HSV-1-specific CD8⁺ T cells by HSV-1 Us3-mediated inhibition of MHC-I antigen presentation might in part contribute to viral replication in vivo.</p> </div