  Vaccinia virus lacking the Bcl-2-like protein N1 induces a stronger natural killer cell response to infection.Jacobs, Nathalie  ; ; et alin Journal of General Virology (The) (2008), 89(Pt 11), 2877-81 The vaccinia virus (VACV) N1 protein is an intracellular virulence factor that has a Bcl-2-like structure and inhibits both apoptosis and signalling from the interleukin 1 receptor, leading to nuclear ... [more ▼] The vaccinia virus (VACV) N1 protein is an intracellular virulence factor that has a Bcl-2-like structure and inhibits both apoptosis and signalling from the interleukin 1 receptor, leading to nuclear factor kappa B activation. Here, we investigated the immune response to intranasal infection with a virus lacking the N1L gene (vDeltaN1L) compared with control viruses expressing N1L. Data presented show that deletion of N1L did not affect the proportion of CD4+ and CD8+ T cells infiltrating the lungs or the cytotoxic T-cell activity of these cells. However, vDeltaN1L induced an increased local natural killer cell activity between days 4 and 6 post-infection. In addition, in the absence of N1 the host inflammatory infiltrate was characterized by a reduced proportion of lymphocytes bearing the early activation marker CD69. Notably, there was a good correlation between the level of CD69 expression and weight loss. The implications of these findings are discussed. [less ▲] Detailed reference viewed: 56 (20 ULg)Camelpox virus encodes a schlafen-like protein that affects orthopoxvirus virulence.; ; et al in Journal of General Virology (The) (2007), 88(Pt 6), 1667-76 Camelpox virus (CMLV) gene 176R encodes a protein with sequence similarity to murine schlafen (m-slfn) proteins. In vivo, short and long members of the m-slfn family inhibited T-cell development, whereas ... [more ▼] Camelpox virus (CMLV) gene 176R encodes a protein with sequence similarity to murine schlafen (m-slfn) proteins. In vivo, short and long members of the m-slfn family inhibited T-cell development, whereas in vitro, only short m-slfns caused arrest of fibroblast growth. CMLV 176 protein (v-slfn) is most closely related to short m-slfns; however, when expressed stably in mammalian cells, v-slfn did not inhibit cell growth. v-slfn is a predominantly cytoplasmic 57 kDa protein that is expressed throughout infection. Several other orthopoxviruses encode v-slfn proteins, but the v-slfn gene is fragmented in all sequenced variola virus and vaccinia virus (VACV) strains. Consistent with this, all 16 VACV strains tested do not express a v-slfn detected by polyclonal serum raised against the CMLV protein. In the absence of a small animal model to study CMLV pathogenesis, the contribution of CMLV v-slfn to orthopoxvirus virulence was studied via its expression in an attenuated strain of VACV. Recombinant viruses expressing wild-type v-slfn or v-slfn tagged at its C terminus with a haemagglutinin (HA) epitope were less virulent than control viruses. However, a virus expressing v-slfn tagged with the HA epitope at its N terminus had similar virulence to controls, implying that the N terminus has an important function. A greater recruitment of lymphocytes into infected lung tissue was observed in the presence of wild-type v-slfn but, interestingly, these cells were less activated. Thus, v-slfn is an orthopoxvirus virulence factor that affects the host immune response to infection. [less ▲] Detailed reference viewed: 46 (3 ULg)Intradermal immune response after infection with Vaccinia virus.Jacobs, Nathalie ; ; et alin Journal of General Virology (The) (2006), 87(Pt 5), 1157-61 Although Vaccinia virus (VACV) was used to eradicate smallpox by dermal vaccination, there is little information available about the immune response induced at the vaccination site. Previously, an ... [more ▼] Although Vaccinia virus (VACV) was used to eradicate smallpox by dermal vaccination, there is little information available about the immune response induced at the vaccination site. Previously, an intradermal murine model that mimics smallpox vaccination was established. Here, this model was used to investigate which leukocytes are recruited to the infected lesion and what are the kinetics of recruitment. Data presented show that VACV infection induced the infiltration of macrophages, followed by granulocytes and lymphocytes. Up to 4 days post-infection, the major lymphocyte population was TCRgammadelta T cells, but thereafter, there was a large recruitment of CD4(+) and CD8(+) T cells. Interestingly, the majority of T cells expressed the natural killer-cell marker DX5. This report is the first to characterize the local immune response sequence to VACV infection and represents a benchmark against which the responses induced by genetically modified VACVs may be compared. [less ▲] Detailed reference viewed: 13 (5 ULg)Vaccinia virus strain Western Reserve protein B14 is an intracellular virulence factor.; Jacobs, Nathalie ; in Journal of General Virology (The) (2006), 87(Pt 6), 1451-8 A characterization of the B14R gene from Vaccinia virus (VACV) strain Western Reserve (WR) is presented. Computational analyses of the B14R gene indicated high conservation in orthopoxviruses but no ... [more ▼] A characterization of the B14R gene from Vaccinia virus (VACV) strain Western Reserve (WR) is presented. Computational analyses of the B14R gene indicated high conservation in orthopoxviruses but no orthologues outside the Poxviridae. To characterize the B14 protein, the B14R gene was expressed in Escherichia coli and recombinant protein was purified and used to generate a rabbit polyclonal antiserum. This antiserum recognized a 15 kDa cytoplasmic protein in mammalian cells that were transfected with the B14R gene or infected with VACV WR, but not from cells infected with a VACV mutant (vdeltaB14) from which the B14R gene was deleted. Compared to wild-type and revertant virus controls, vdeltaB14 had normal growth kinetics in cell culture. The virulence of vdeltaB14 was assessed in two in vivo models. Mice infected intranasally with vdeltaB14 had similar weight loss compared to the controls, but in C57BL/6 mice infected intradermally vdeltaB14 induced a smaller lesion size compared with controls. Moreover, intradermal infection with vdeltaB14 caused an increased infiltration of cells into the infected lesion despite the smaller lesion size. Therefore, B14 is an intracellular protein that is non-essential for virus replication in cell culture but contributes to virus virulence in vivo and affects the host response to infection. [less ▲] Detailed reference viewed: 27 (2 ULg) |
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