Abstract
Human cytomegalovirus (HCMV), a common herpes virus, has been reported to be a risk factor for many diseases, including malignant diseases such as glioma, neuroblastoma, and breast cancer. Some of the HCMV-associated diseases (e.g., glioma) are rare. The question arises: how could a common virus be associated with uncommon diseases? Interactions between a major gene complex of the human immune system and a viral immunoevasion strategy – a probable mechanism of their co-evolutionary adaptation – may shed light on this paradox. To ensure its survival, HCMV has evolved sophisticated immunoevasion strategies. One strategy involves encoding decoy Fcγ receptors (FcγR), which may enable the virus to evade host immunosurveillance by avoiding the Fcγ-mediated effector consequences of anti-HCMV IgG antibody binding. Immunoglobulin G1 proteins expressing GM (γ marker) alleles 3 and 17 have differential affinity to the HCMV TRL11/IRL11-encoded FcγR, and thus act as effect modifiers of HCMV-associated malignancies. The high affinity GM 3 allele has been shown to be a risk factor for neuroblastoma, glioma, and breast cancer. Additional studies involving other viral FcγRs as well as GM alleles expressed on other IgG subclasses are warranted.
Highlights
Immunoglobulin (Ig) GM (γ marker) allotypes are encoded by three very closely linked genes – Ig heavy chain G1 (IGHG1), IGHG2, and IGHG3 – on chromosome 14q32
We have shown that Human cytomegalovirus (HCMV) TRL11/IRL11encoded Fcγ receptors (FcγR) has significantly higher affinity for IgG1 proteins expressing the GM 3+,1−,2− allotypes than for those expressing the allelic GM 17+,1+,2+ allotypes (p = 0.0005)
To gain further mechanistic insights into the GM gene involvement in the pathogenesis of this malignancy, it would be necessary to evaluate the affinity of viral FcγRs to the IgG proteins expressing other GM alleles – 1, 5, and 21 – that constitute the genotypes associated with neuroblastoma
Summary
Immunoglobulin (Ig) GM (γ marker) allotypes are encoded by three very closely linked genes – Ig heavy chain G1 (IGHG1), IGHG2, and IGHG3 – on chromosome 14q32. We have shown that HCMV TRL11/IRL11encoded FcγR has significantly higher affinity for IgG1 proteins expressing the GM 3+,1−,2− allotypes than for those expressing the allelic GM 17+,1+,2+ allotypes (p = 0.0005).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
