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Persistent infections and their relationship with selected oncologic and non-tumor pathologies
Anatolii A Chumak1, Irina V Abramenko, Nadia I Bilous
1S.I. Research Centre for Radiation Medicine, Kyiv, Ukraine. papatolia@mail.ru
Insights
Viral infections like hepatitis C virus (HCV) and cytomegalovirus (CMV) can worsen health conditions and promote leukemia in Chernobyl survivors. Ionizing radiation exposure may also influence these outcomes.
Area of Science:
- Virology
- Radiation Oncology
- Immunology
Background:
- Hepatitis C virus (HCV) and cytomegalovirus (CMV) prevalence was previously found to be 3.45% in healthy blood donors.
- Chernobyl NPP accident sufferers experienced acute radiation syndrome (ARS).
- High incidence of chronic lymphocytic leukemia (CLL) observed among Chernobyl sufferers.
Purpose of the Study:
- To analyze HCV and CMV prevalence in individuals exposed to ionizing radiation (IR) due to the Chernobyl NPP accident.
- To investigate the association between viral infections and somatic diseases or malignancies in exposed and non-exposed individuals.
- To explore homology between immunoglobulins (Igs) in CLL patients and antiviral/antimicrobial Igs.
Main Methods:
- Serological analyses using enzyme-linked immunosorbent assay (ELISA) for antibodies against HCV and CMV.
- Polymerase chain reaction (PCR) analyses of Ig heavy-chain variable (IgHV) genes in CLL patients.
- Comparison of viral prevalence and disease incidence between Chernobyl accident sufferers (cleanup workers, residents, NPP workers, convalescent patients) and IR-non-exposed controls.
Main Results:
- Highest HCV (27.2%) and CMV (85.6%) prevalence observed in convalescent ARS patients.
- HCV prevalence in cleanup workers ranged from 11-25% and was associated with increased incidence of somatic diseases like thyroiditis, goiter, hypertension, Type 1 diabetes, and chronic hepatitis/gastritis.
- CMV association found with chronic gastritis, arthritis, and bronchitis in cleanup workers and controls.
- Clear delineation in pathology incidence based on 1986 IR exposure, irrespective of CMV status.
- Significant homology found between some IgHV genes in CLL patients and Igs against infectious agents, with no difference between IR-exposed and non-exposed groups.
Conclusions:
- Past or ongoing viral infections (CMV, HCV) can aggravate clinical courses of somatic diseases and promote malignancies like CLL.
- These outcomes may be modulated by prior exposure to ionizing radiation.
- Homology in IgHV genes suggests a potential link between immune responses to infections and CLL development in Chernobyl survivors.
Abstract:
Our earlier studies of hepatitis C virus (HCV) infection rates among blood donors at the Kyiv Municipal Blood Center revealed a 3.45% HCV+ prevalence in these "healthy" hosts. In the study here, we analyzed HCV (as well as cytomegalovirus [CMV]) prevalence among Chernobyl nuclear power plant (NPP) accident sufferers--cleanup workers, local residents, NPP workers, and convalescent patients--who suffered acute radiation syndrome (ARS) as a result of the 1986 accident, and individuals who had not been exposed to ionizing radiation (IR). Serological analyses of antibodies against each pathogen (via enzyme-linked immunosorbent assay [ELISA]) revealed the highest HCV (i.e., 27.2%) and CMV (85.6%) prevalence in the convalescent hosts. Though the HCV prevalence (reflecting a current/past infection) among the cleanup workers (and other groups) was lower (i.e., 11-25%), viral presence was "associated" with a higher incidence of selected somatic diseases, for example, thyroiditis, goiter, hypertension, Type 1 diabetes, chronic hepatitis/gastritis, in the cleanup workers. A similar scenario with respect to CMV was also seen, i.e., lower prevalence rates [relative to in ARS patients] and "association" between CMV status and incidence of chronic gastritis, arthritis, and bronchitis, in the cleanup workers and IR-non-exposed controls. Further, irrespective of CMV status, there was a clear delineation between incidence rate(s) of each of the pathologies and whether or not the person was/was not exposed in 1986. We also investigated, due to a high incidence of chronic lymphocytic leukemia (CLL) among Chernobyl sufferers, if there was homology between immunoglobulins (Igs) generated by these transformed cells and known antiviral and antimicrobial Igs. Polymerase chain reaction (PCR) analyses of Ig heavy-chain variable (IgHV) genes in cells from CLL patients who were/were not exposed in 1986 revealed a significant homology of some IgHV genes with Igs directed against infectious agents. However, no differences were found between the sequences from IR-exposed and IR-non-exposed CLL patients. Based on the findings here, we conclude that a past/ongoing presence of certain viral infections (i.e., CMV and/or HCV) in a host can modify (aggravate) the clinical course of certain somatic (i.e., non-tumor) diseases and promote malignancies (i.e., CLL), and that each of these outcomes could be modulated as a result of that host's past exposure to IR.
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