Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, ...N6-methyladenosine (m6A) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. m6A methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether m6A is also involved in viral entry and whether m6A can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify m6A reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for m6A methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection.
T cell activation is a highly regulated process, modulated via the expression of various immune regulatory proteins including cytokines, surface receptors and co-stimulatory proteins. ...N6-methyladenosine (m6A) is an RNA modification that can directly regulate RNA expression levels and it is associated with various biological processes. However, the function of m6A in T cell activation remains incompletely understood. We identify m6A as a novel regulator of the expression of the CD40 ligand (CD40L) in human CD4+ lymphocytes. Manipulation of the m6A ‘eraser’ fat mass and obesity-associated protein (FTO) and m6A ‘writer’ protein methyltransferase-like 3 (METTL3) directly affects the expression of CD40L. The m6A ‘reader’ protein YT521-B homology domain family-2 (YTHDF2) is hypothesized to be able to recognize and bind m6A specific sequences on the CD40L mRNA and promotes its degradation. This study demonstrates that CD40L expression in human primary CD4+ T lymphocytes is regulated via m6A modifications, elucidating a new regulatory mechanism in CD4+ T cell activation that could possibly be leveraged in the future to modulate T cell responses in patients with immune-related diseases.
T cell activation is a highly regulated process, modulated via the expression of various immune regulatory proteins including cytokines, surface receptors and co-stimulatory proteins. N
...-methyladenosine (m
A) is an RNA modification that can directly regulate RNA expression levels and it is associated with various biological processes. However, the function of m
A in T cell activation remains incompletely understood. We identify m
A as a novel regulator of the expression of the CD40 ligand (CD40L) in human CD4
lymphocytes. Manipulation of the m
A 'eraser' fat mass and obesity-associated protein (FTO) and m
A 'writer' protein methyltransferase-like 3 (METTL3) directly affects the expression of CD40L. The m
A 'reader' protein YT521-B homology domain family-2 (YTHDF2) is hypothesized to be able to recognize and bind m
A specific sequences on the
mRNA and promotes its degradation. This study demonstrates that CD40L expression in human primary CD4
T lymphocytes is regulated via m
A modifications, elucidating a new regulatory mechanism in CD4
T cell activation that could possibly be leveraged in the future to modulate T cell responses in patients with immune-related diseases.
The tight regulation of the expression of cytokines, surface receptors and co-stimulatory and co-inhibitory molecules is necessary for a well-functioning immune system. There are various cellular ...processes that regulate the expression of these immune regulatory proteins, for instance at the RNA transcript level. Epitranscriptomic regulation, involving RNA binding proteins and modifications, can determine the turnover and translation of mRNA transcripts. Nsup.6-methyladenosine (msup.6A) is the most abundant RNA modification in eukaryotic cells and it was demonstrated that msup.6A is involved in the early differentiation of CD4sup.+ T lymphocytes. However, the function of msup.6A in CD4sup.+ T cell activation and function is still incompletely understood. Here, we demonstrate that msup.6A regulates the activation of CD4sup.+ T lymphocytes via the regulation of CD40 ligand expression, a key co-stimulatory molecule expressed on the cell surface of CD4sup.+ T cells. The discovery of this novel function of msup.6A and its regulatory proteins contributes to our general understanding of CD4sup.+ T cell activation, gene expression regulation and autoimmune disease pathogenesis. T cell activation is a highly regulated process, modulated via the expression of various immune regulatory proteins including cytokines, surface receptors and co-stimulatory proteins. Nsup.6-methyladenosine (msup.6A) is an RNA modification that can directly regulate RNA expression levels and it is associated with various biological processes. However, the function of msup.6A in T cell activation remains incompletely understood. We identify msup.6A as a novel regulator of the expression of the CD40 ligand (CD40L) in human CD4sup.+ lymphocytes. Manipulation of the msup.6A ‘eraser’ fat mass and obesity-associated protein (FTO) and msup.6A ‘writer’ protein methyltransferase-like 3 (METTL3) directly affects the expression of CD40L. The msup.6A ‘reader’ protein YT521-B homology domain family-2 (YTHDF2) is hypothesized to be able to recognize and bind msup.6A specific sequences on the CD40L mRNA and promotes its degradation. This study demonstrates that CD40L expression in human primary CD4sup.+ T lymphocytes is regulated via msup.6A modifications, elucidating a new regulatory mechanism in CD4sup.+ T cell activation that could possibly be leveraged in the future to modulate T cell responses in patients with immune-related diseases.
Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, ...N6-methyladenosine (msup.6A) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. msup.6A methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether msup.6A is also involved in viral entry and whether msup.6A can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify msup.6A reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for msup.6A methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection.
Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, ...N6-methyladenosine (m
A) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. m
A methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether m
A is also involved in viral entry and whether m
A can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify m
A reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for m
A methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection.
