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Complement-fixing antibodies to human cytomegalovirus induced early nuclear antigens in mononucleosis
Abstract:
Early nuclear antigen (CMNA) induced by human cytomegalovirus (HCMV) was extracted from infected human embryonic fibroblast cells and purified by ds DNA Sephadex chromatography. The purified antigen was added to acid-fixed preparations from human embryonic fibroblasts and these in vitro converted nuclei were exposed to human sera to estimate the antibodies to CMNA by anti-complement immunofluorescence staining. Serial serum samples were obtained from eight patients suffering from acute HCMV infection (mononucleosis), from nine patients with Epstein-Barr virus (EBV) mononucleosis, and from 20 healthy persons who had been shown to possess antibodies to HCMV late antigens. Acute HCMV infection is characterized by the presence of anti-CMNA antibodies at high titer (1:16 - 1:32) together with the elevated level of IgG antibodies to anti-HCMV-late antigens. During convalescence the anti-CMNA titer decreased to a lower level which was maintained for long period. The anti-CMNA antibodies were also regularly detected in sera of persons possessing antibodies to HCMV late antigens but without any sign of acute HCMV infection. It is concluded that antibodies to CMNA are not transitory and their presence even at high titer (1:16 - 1:32) in a serum sample cannot be taken as a presumptive evidence of acute virus infection. This method seems to be valuable for measuring antibodies to nuclear DnA-binding antigens induced by other viruses.
Insights
Antibodies to early nuclear antigen (CMNA) from human cytomegalovirus (HCMV) are not transient. High titers of anti-CMNA antibodies do not definitively indicate acute HCMV infection.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Human cytomegalovirus (HCMV) infection is a significant public health concern.
- Understanding immune responses to HCMV, including antibodies to early viral antigens, is crucial for diagnosis and management.
- Previous studies have focused on antibodies to late HCMV antigens, with less known about early nuclear antigen (CMNA) antibodies.
Purpose of the Study:
- To characterize antibodies to early nuclear antigen (CMNA) induced by human cytomegalovirus (HCMV).
- To evaluate the diagnostic significance of anti-CMNA antibodies in acute HCMV infections.
- To assess the utility of anti-CMNA antibodies as potential biomarkers for viral infections.
Main Methods:
- Extraction and purification of CMNA from HCMV-infected human embryonic fibroblast cells.
- Development of an in vitro assay using acid-fixed cells and human sera for antibody detection.
- Anti-complement immunofluorescence staining to quantify antibodies to CMNA.
- Analysis of serial serum samples from patients with acute HCMV infection, Epstein-Barr virus mononucleosis, and healthy individuals.
Main Results:
- Acute HCMV infection showed high titers (1:16 - 1:32) of anti-CMNA antibodies alongside elevated IgG antibodies to HCMV late antigens.
- Anti-CMNA antibody titers decreased during convalescence and remained at lower levels long-term.
- Anti-CMNA antibodies were consistently detected in individuals with prior HCMV exposure but without signs of acute infection.
Conclusions:
- Antibodies to CMNA are persistent and not transient markers of acute HCMV infection.
- High titers of anti-CMNA antibodies alone are insufficient for diagnosing acute HCMV infection.
- The developed method for detecting anti-CMNA antibodies may be valuable for identifying antibodies to nuclear DNA-binding antigens induced by other viruses.