The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform

Bernard Moss - One of the best experts on this subject based on the ideXlab platform.

  • molluscum contagiosum virus interleukin 18 il 18 binding protein is secreted as a full length form that binds cell surface glycosaminoglycans through the c terminal tail and a furin cleaved form with only the il 18 binding domain
    Journal of Virology, 2003
    Co-Authors: Yan Xiang, Bernard Moss
    Abstract:

    Molluscum contagiosum virus (MCV) and variola virus are the sole members of the poxvirus family that use humans as exclusive natural hosts (8). Variola virus belongs to the Orthopoxvirus genus and until recently caused smallpox, an acute infection with a high mortality rate (9). MCV, the only member of the Molluscipoxvirus genus, causes small, benign skin lesions in children and young adults and more extensive disease only when there is a concurrent immunodeficiency such as AIDS (10). Even in immunocompetent individuals, however, the virus-filled skin lesions frequently persist for many months with few signs of inflammation, suggesting local immune suppression. Several potential immune evasion proteins were discovered after the complete MCV genome sequence was determined (17). One of these is an interleukin-18 (IL-18) binding protein (IL-18BP) that inhibits the gamma interferon-inducing activity of IL-18 (25). IL-18 is a proinflammatory cytokine that enhances innate and acquired immunity and protects against microbial infections and tumors in murine models (6). Excessive IL-18 activity, however, is associated with some autoimmune and inflammatory diseases (13). Regulation of IL-18 activity is mediated by soluble IL-18BPs (14, 24). MC54L, an MCV homolog of mammalian IL-18BP, binds IL-18 with a nanomolar Kd and inhibits the gamma interferon-inducing activity of IL-18 in a dose-dependent manner (22, 25). Functional homologs of IL-18BP are also present in orthopoxviruses, including vaccinia virus, cowpox virus, and ectromelia virus (1, 3, 19), and as yet uncharacterized homologs are encoded by variola virus and members of other poxvirus genera. Deletion of the IL-18BP gene from ectromelia virus decreased virus replication and elevated natural killer cell activity in infected mice, indicating that these proteins contribute to defense against the host immune system (1). The IL-18 binding sites of human IL-18BP and MC54L were determined through site-directed mutagenesis and quantitative binding studies (22, 23). Despite the relatively low overall sequence identity between MC54L and human IL-18BP, their IL-18 binding sites are almost identical. MC54L, however, is unique among poxvirus and mammalian IL-18BPs in having a C-terminal tail that is almost 100 amino acids long and is entirely dispensable for IL-18 binding (22). Our present studies show that the protein is secreted in two forms: a full-length form that binds cell surface glycosaminoglycans with high affinity through the C-terminal tail and a furin-cleaved form consisting solely of the IL-18 binding domain (IL-18BD). The long and short forms of MC54L may inhibit IL-18 near the site of infection and at more distal locations, respectively.

Yan Xiang - One of the best experts on this subject based on the ideXlab platform.

  • molluscum contagiosum virus interleukin 18 il 18 binding protein is secreted as a full length form that binds cell surface glycosaminoglycans through the c terminal tail and a furin cleaved form with only the il 18 binding domain
    Journal of Virology, 2003
    Co-Authors: Yan Xiang, Bernard Moss
    Abstract:

    Molluscum contagiosum virus (MCV) and variola virus are the sole members of the poxvirus family that use humans as exclusive natural hosts (8). Variola virus belongs to the Orthopoxvirus genus and until recently caused smallpox, an acute infection with a high mortality rate (9). MCV, the only member of the Molluscipoxvirus genus, causes small, benign skin lesions in children and young adults and more extensive disease only when there is a concurrent immunodeficiency such as AIDS (10). Even in immunocompetent individuals, however, the virus-filled skin lesions frequently persist for many months with few signs of inflammation, suggesting local immune suppression. Several potential immune evasion proteins were discovered after the complete MCV genome sequence was determined (17). One of these is an interleukin-18 (IL-18) binding protein (IL-18BP) that inhibits the gamma interferon-inducing activity of IL-18 (25). IL-18 is a proinflammatory cytokine that enhances innate and acquired immunity and protects against microbial infections and tumors in murine models (6). Excessive IL-18 activity, however, is associated with some autoimmune and inflammatory diseases (13). Regulation of IL-18 activity is mediated by soluble IL-18BPs (14, 24). MC54L, an MCV homolog of mammalian IL-18BP, binds IL-18 with a nanomolar Kd and inhibits the gamma interferon-inducing activity of IL-18 in a dose-dependent manner (22, 25). Functional homologs of IL-18BP are also present in orthopoxviruses, including vaccinia virus, cowpox virus, and ectromelia virus (1, 3, 19), and as yet uncharacterized homologs are encoded by variola virus and members of other poxvirus genera. Deletion of the IL-18BP gene from ectromelia virus decreased virus replication and elevated natural killer cell activity in infected mice, indicating that these proteins contribute to defense against the host immune system (1). The IL-18 binding sites of human IL-18BP and MC54L were determined through site-directed mutagenesis and quantitative binding studies (22, 23). Despite the relatively low overall sequence identity between MC54L and human IL-18BP, their IL-18 binding sites are almost identical. MC54L, however, is unique among poxvirus and mammalian IL-18BPs in having a C-terminal tail that is almost 100 amino acids long and is entirely dispensable for IL-18 binding (22). Our present studies show that the protein is secreted in two forms: a full-length form that binds cell surface glycosaminoglycans with high affinity through the C-terminal tail and a furin-cleaved form consisting solely of the IL-18 binding domain (IL-18BD). The long and short forms of MC54L may inhibit IL-18 near the site of infection and at more distal locations, respectively.

Antonio Alcamı - One of the best experts on this subject based on the ideXlab platform.

  • Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins.
    Microbiology, 2000
    Co-Authors: Vincent P. Smith, Neil A. Bryant, Antonio Alcamı
    Abstract:

    Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-γ (IFN-γ). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-κB activation and induction of IFN-γ in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a Molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections in the host, emphasizes the importance of IL-18 in response to viral infections.

  • Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins
    2000
    Co-Authors: Vincent P. Smith, Neil A. Bryant, Antonio Alcamı
    Abstract:

    Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-c (IFN-c). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-jB activation and induction of IFN-c in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a Molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections i

Vincent P. Smith - One of the best experts on this subject based on the ideXlab platform.

  • Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins.
    Microbiology, 2000
    Co-Authors: Vincent P. Smith, Neil A. Bryant, Antonio Alcamı
    Abstract:

    Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-γ (IFN-γ). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-κB activation and induction of IFN-γ in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a Molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections in the host, emphasizes the importance of IL-18 in response to viral infections.

  • Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins
    2000
    Co-Authors: Vincent P. Smith, Neil A. Bryant, Antonio Alcamı
    Abstract:

    Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-c (IFN-c). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-jB activation and induction of IFN-c in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a Molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections i

Neil A. Bryant - One of the best experts on this subject based on the ideXlab platform.

  • Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins.
    Microbiology, 2000
    Co-Authors: Vincent P. Smith, Neil A. Bryant, Antonio Alcamı
    Abstract:

    Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-γ (IFN-γ). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-κB activation and induction of IFN-γ in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a Molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections in the host, emphasizes the importance of IL-18 in response to viral infections.

  • Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins
    2000
    Co-Authors: Vincent P. Smith, Neil A. Bryant, Antonio Alcamı
    Abstract:

    Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-c (IFN-c). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-jB activation and induction of IFN-c in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a Molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections i