ArticlePLoS pathogens2008
Surviving mousepox infection requires the complement system.
Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Monoclonal Antibodies in Light of Mpox Outbreak: Current Research, Therapeutic Targets, and Animal Models.Antibodies (Basel, Switzerland) · 2025Review
- The monkeypox virus-host interplays.Cell insight · 2024Review
- A comprehensive review of monkeypox virus and mpox characteristics.Frontiers in cellular and infection microbiology · 2024Review
- The recent re-emergence of human monkeypox: Would it become endemic beyond Africa?Journal of infection and public health · 2023Review
- Orthopoxvirus Zoonoses-Do We Still Remember and Are Ready to Fight?Pathogens (Basel, Switzerland) · 2023Review
- The prospective outcome of the monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology.Frontiers in cellular and infection microbiology · 2023Article
- Poxviruses and the immune system: Implications for monkeypox virus.International immunopharmacology · 2022Review
- Monkeypox: disease epidemiology, host immunity and clinical interventions.Nature reviews. Immunology · 2022Review
- Protective role of host complement system inFrontiers in immunology · 2022Article
- A Dual Role of Complement Activation in the Development of Fulminant Hepatic Failure Induced by Murine-Beta-Coronavirus Infection.Frontiers in cellular and infection microbiology · 2022Article
- New insights into the immunomodulatory properties of poxvirus cytokine decoy receptors at the cell surface.F1000Research · 2018Review
- Viral-derived complement inhibitors: current status and potential role in immunomodulation.Experimental biology and medicine (Maywood, N.J.) · 2017Review
- Complement Evasion Strategies of Viruses: An Overview.Frontiers in microbiology · 2017Review
- Successive site translocating inoculation potentiates DNA/recombinant vaccinia vaccination.Scientific reports · 2015Article
- Evidence for Persistence of Ectromelia Virus in Inbred Mice, Recrudescence Following Immunosuppression and Transmission to Naïve Mice.PLoS pathogens · 2015Article
- Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial.Open forum infectious diseases · 2015Article
- Inhibitors of C5 complement enhance vaccinia virus oncolysis.Cancer gene therapy · 2013Article
- Coagulation factor X shields adenovirus type 5 from attack by natural antibodies and complement.Nature medicine · 2013Article
- Unusual features of vaccinia virus extracellular virion form neutralization resistance revealed in human antibody responses to the smallpox vaccine.Journal of virology · 2013Article
- Hepatitis C virus NS3/4A protease inhibits complement activation by cleaving complement component 4.PloS one · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Poxviruses subvert the host immune response by producing immunomodulatory proteins, including a complement regulatory protein. Ectromelia virus provides a mouse model for smallpox where the virus and the host's immune response have co-evolved. Using this model, our study investigated the role of the complement system during a poxvirus infection. By multiple inoculation routes, ectromelia virus caused increased mortality by 7 to 10 days post-infection in C57BL/6 mice that lack C3, the central component of the complement cascade. In C3(-/-) mice, ectromelia virus disseminated earlier to target organs and generated higher peak titers compared to the congenic controls. Also, increased hepatic inflammation and necrosis correlated with these higher tissue titers and likely contributed to the morbidity in the C3(-/-) mice. In vitro, the complement system in naïve C57BL/6 mouse sera neutralized ectromelia virus, primarily through the recognition of the virion by natural antibody and activation of the classical and alternative pathways. Sera deficient in classical or alternative pathway components or antibody had reduced ability to neutralize viral particles, which likely contributed to increased viral dissemination and disease severity in vivo. The increased mortality of C4(-/-) or Factor B(-/-) mice also indicates that these two pathways of complement activation are required for survival. In summary, the complement system acts in the first few minutes, hours, and days to control this poxviral infection until the adaptive immune response can react, and loss of this system results in lethal infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.