Complement and viral pathogenesis.

Department of Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Virology (Impact Factor: 3.28). 02/2011; 411(2):362-73. DOI: 10.1016/j.virol.2010.12.045
Source: PubMed

ABSTRACT The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection.

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    ABSTRACT: Background and study aims To search for an immunological parameter that may correlate with the response to interferon (IFN) treatment is very crucial. The objective of this study was to correlate the levels of C3 and C4 complement components with the response to IFN treatment in patients with chronic hepatitis C virus (HCV) infection. Patients and methods This study was conducted on 100 patients and control subjects classified into three groups. Group (I) consisted of 50 patients with chronic hepatitis C who were receiving IFN treatment and showed various responses; group (II) included 25 patients with chronic hepatitis C naive to IFN treatment; and group (III) included 25 healthy subjects matched for age and sex who served as controls. Measurement of the level of complement C3 and C4 was done by a quantitative turbidimetric test. Measurement of complement levels in group (I) was done at the end of treatment at the 48th week. Results Serum levels of C3 and C4 were found to be significantly reduced in all patients with chronic HCV infection in both groups (I and II) compared to the healthy control group (III) (p < 0.05). Moreover, chronic HCV patients treated with IFN and ribavirin had significantly lower levels of C3 and C4 compared with patients naive to IFN and ribavirin treatment. At the end of treatment, both C3 and C4 had significantly increased in responders to IFN when compared to non-responders (p = 0.025 and 0.05, respectively). There was a significant negative correlation between C3 and C4 levels and the concentration of serum alanine aminotransferase (ALT) measured simultaneously. Conclusion Higher C3 and C4 serum concentrations were found to be positively correlated to the end-of-treatment response in patients with chronic HCV infection treated with IFN and ribavirin.
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    ABSTRACT: The African Green Monkey (AGM) model was used to analyze the role of complement in neutralization of parainfluenza virus. Parainfluenza virus 5 (PIV5) and human parainfluenza virus type 2 were effectively neutralized in vitro by naïve AGM sera, but neutralizing capacity was lost by heat-inactivation. The mechanism of neutralization involved formation of massive aggregates, with no evidence of virion lysis. Following inoculation of the respiratory tract with a PIV5 vector expressing HIV gp160, AGM produced high levels of serum and tracheal antibodies against gp120 and the viral F and HN proteins. However, in the absence of complement these anti-PIV5 antibodies had very poor neutralizing capacity. Virions showed extensive deposition of IgG and C1q with post- but not pre-immune sera. These results highlight the importance of complement in the initial antibody response to parainfluenza viruses, with implications for understanding infant immune responses and design of vaccine strategies for these pediatric pathogens.
    Virology 07/2014; s 460–461:23–33. · 3.28 Impact Factor
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    ABSTRACT: Cancer is a traitorous archenemy that threatens our survival. Its ability to evade detection and adapt to various cancer therapies means that it is a moving target that becomes increasingly difficult to attack. Through technological advancements, we have developed sophisticated weapons to fight off tumor growth and invasion. However, if we are to stand a chance in this war against cancer, advanced tactics will be required to maximize the use of our available resources. Oncolytic viruses (OVs) are multi-functional cancer-fighters that can be engineered to suit many different strategies; in particular, their retooling can facilitate increased capacity for direct tumor killing (oncolytic virotherapy) and elicit adaptive antitumor immune responses (oncolytic immunotherapy). However, administration of these modified OVs alone, rarely induces successful regression of established tumors. This may be attributed to host antiviral immunity that acts to eliminate viral particles, as well as the capacity for tumors to adapt to therapeutic selective pressure. It has been shown that various chemotherapeutic drugs with distinct functional properties can potentiate the antitumor efficacy of OVs. In this review, we summarize the chemotherapeutic combinatorial strategies used to optimize virally induced destruction of tumors. With a particular focus on pharmaceutical immunomodulators, we discuss how specific therapeutic contexts may alter the effects of these synergistic combinations and their implications for future clinical use.
    Frontiers in Oncology 06/2014; 4:145.


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