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HCMV-encoded UL128 enhances TNF-α and IL-6 expression and promotes PBMC proliferation through the MAPK/ERK pathway in

Qi Zheng1, Ran Tao, Huihui Gao

  • 1Department of Pediatrics, Children's Hospital Affiliated with the Medical College, Zhejiang University, Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Hangzhou, China.

Viral Immunology
|April 11, 2012
PubMed

Insights

Human cytomegalovirus (HCMV) UL128 protein enhances inflammatory mediators like IL-6 and TNF-α, promoting virus replication. This study clarifies UL128

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Cytomegalovirus (CMV) infection modulates host immune responses by altering cytokine expression.
  • The specific viral proteins responsible for inducing certain cytokine productions during CMV infection remain largely uncharacterized.
  • CMV encodes proteins that can interfere with or mimic host leukocyte functions.

Purpose of the Study:

  • To investigate the role of the human CMV (HCMV)-encoded UL128 protein in modulating cytokine production and cellular responses.
  • To determine if UL128 protein influences the expression of key inflammatory cytokines.
  • To explore the involvement of the MAPK/ERK pathway in UL128-mediated cellular effects.

Main Methods:

  • Utilized RNA interference to create HCMV (UL128-positive/UL128-negative) infected tissue cell (MRC-5) and peripheral blood mononuclear cell (PBMC) co-cultures.
  • Quantified levels of six cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) in culture supernatants.
  • Assessed PBMC viability upon exposure to UL128 protein and analyzed the involvement of the MAPK/ERK pathway.

Main Results:

  • HCMV UL128-positive infections showed significantly elevated levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) compared to UL128-knockout groups.
  • PBMCs treated with UL128 protein exhibited enhanced cell viability.
  • The MAPK/ERK pathway was identified as being involved in UL128-induced cell proliferation.

Conclusions:

  • The HCMV-encoded UL128 protein acts as a significant inducer of specific inflammatory mediators, including IL-6 and TNF-α.
  • UL128 contributes to enhanced cell viability and proliferation, potentially through the MAPK/ERK pathway.
  • Understanding UL128's role provides insights into HCMV pathogenesis and immune evasion strategies.

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