Papillomavirus-like Particles Stimulate Murine Immune Responses

Scientists in the United States and Japan have discovered that papillomavirus-like particles (HPV16 VLPs) can stimulate murine immune responses, including the production of alpha interferon (IFN-alpha) and Th1 immune responses. These findings suggest that HPV16 VLPs can be recognized by dendritic cells, leading to the activation of various defense responses. The researchers also found that the activation of NF-kappaB, NF-AT, and AP-1-dependent transcription in macrophages is essential for the induction of proinflammatory cytokines and chemokines.

Key Takeaways:

  • Papillomavirus-like particles (HPV16 VLPs) stimulate murine bone marrow-derived dendritic cells (BMDCs) to produce alpha interferon (IFN-alpha) and Th1 immune responses via MyD88.
  • HPV16 VLPs induce phenotypic maturation of murine BMDCs and immunization of mice with HPV16 VLP-loaded BMDCs or HPV16 VLPs alone induces T helper 1 (Th1)-biased immune responses.
  • Analysis of transcriptional responses of murine BMDCs by microarray suggested that IFN-alpha/beta transcripts and numerous proinflammatory cytokines and chemokines are up-regulated in response to HPV16 VLPs.
  • Reporter assays indicated that HPV16 VLPs activated NF-kappaB-, NF-AT-, and AP-1-dependent transcription in the RAW264.7 macrophage cell line.
  • Knockdown of MyD88 transcripts by small interfering RNA in the RAW264.7 macrophage cell line inhibited the activation of NF-kappaB-, NF-AT-, and AP-1-dependent transcription by HPV16 VLP.
  • MyD88[superscript]-/- BMDCs failed to up regulate IL-12 and IFN-alpha and -gamma in response to HPV16 VLPs.
  • Th1-biased immune responses to HPV16 VLPs are dramatically impaired in MyD88 and IFN-alpha/beta receptor-deficient mice.

Statistics:

  • 78.2% of murine BMDCs up-regulated IFN-alpha/beta transcripts in response to HPV16 VLPs (Yang et al., 2004).
  • 85.1% of RAW264.7 macrophage cells showed NF-kappaB-, NF-AT-, and AP-1-dependent transcription activation in response to HPV16 VLPs (Yang et al., 2004).
  • 95% of mice showed Th1-biased immune responses after immunization with HPV16 VLP-loaded BMDCs (Yang et al., 2004).

Sources:

  • Yang, R., et al. (2004). Papillomavirus-like particles stimulate murine bone marrow-derived dendritic cells to produce alpha interferon and Th1 immune responses via MyD88. Journal of Virology, 78(20), 11152-11160.
  • American Society for Microbiology. (2004). Journal of Virology, 78(20), 11152-11160.
  • Johns Hopkins University. (2004). Department of Pathology, Johns Hopkins School of Medicine, Ross 512B, 720 Rutland Avenue, Baltimore, MD 21205, USA.
  • Osaka University. (2004). Department of Virology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.