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. 2008 Nov;89(Pt 11):2877-2881.
doi: 10.1099/vir.0.2008/004119-0.

Vaccinia virus lacking the Bcl-2-like protein N1 induces a stronger natural killer cell response to infection

Nathalie Jacobs  1 , Nathan W Bartlett  1 , Richard H Clark  1 , Geoffrey L Smith  1
Affiliations

Vaccinia virus lacking the Bcl-2-like protein N1 induces a stronger natural killer cell response to infection

Nathalie Jacobs et al. J Gen Virol. 2008 Nov.

Abstract

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.

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Figures

Fig. 1.
Fig. 1.
NK cells after intranasal infection with WT, vΔN1L and Rev. (a) The percentages of NK cells (% of CD3−DX5+ in lymphocyte gate) in the lung. Data shown are means±sem of four experiments. (b) Percentages of NK cells (% of CD3−DX5+ in lymphocyte gate) in BAL of one experiment with pooled data from four mice. (c) Chromium release assay of cells isolated from infected lung against NK-sensitive Yac cells. Data shown are means±sem of two experiments (E : T=effector : target ratio; the test is measured in triplicate).
Fig. 2.
Fig. 2.
The N1L protein contributes to virulence in an intranasal infection model. Groups of five female BALB/c mice (6–8 weeks of age) were infected intranasally with 104 p.f.u. of the indicated virus. On days 3, 7 and 10 lungs were harvested and assayed for infectious virus by plaque assay. The data are expressed as means±sem. The data were analysed by log-transforming followed by one-way ANOVA. Bonferroni's post-test with 95 % confidence levels (Prism 4 GraphPad) was used to pin-point significant differences. *, P<0.05; **, P<0.01 for vΔN1L compared with WT and Rev.
Fig. 3.
Fig. 3.
CD69 expression on lung cells after intranasal infection with WT, vΔN1L and Rev. (a) CD69 expression in lung (lymphocytes gate). Data are means±sem of two independent experiments. *, P<0.05; **, P<0.01. (b) Correlation between per cent weight loss and per cent of CD69-positive cells in the lungs at day 6 p.i. P<0.0001.
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