Potential inhibition of somatic hypermutation by nucleoside analogues.
Somatic hypermutation, which occurs in antigen-activated germinal centre B lymphocytes, diversifies the genes that encode immunoglobulin variable regions and leads to the 'affinity maturation' of the humoral immune response. Hypermutation affects dC/dG and dA/dT pairs with approximately equal frequency in vivo. DNA polymerase-theta contributes to hypermutagenesis at dC/dG pairs and DNA polymerase-eta is substantially involved in the generation of hypermutations at dA/dT pairs. The biochemical properties of polymerases-theta and -eta indicate that their DNA synthetic activities are potentially susceptible to inhibition by nucleoside analogues, so it is feasible that nucleoside analogues reduce the accumulation of dC/dG- and dA/dT-targeted hypermutations in vivo. Nucleoside analogues could hence impair the humoral adaptive immune response of HIV-infected patients who are prescribed these chemotherapeutic agents.
Franklin
Andrew
A
Biocontrol Group, School of Botany and Zoology, Australian National University, Daley Road, Acton, 0200 ACT, Australia. Andrew.Franklin@anu.edu.au
Blanden
Robert V
RV
D001402:B-Lymphocytes / Q000276:immunology; D004261:DNA Replication / Q000276:immunology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D009705:Nucleosides / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D027041:Somatic Hypermutation, Immunoglobulin / Q000187:drug effects; D000097462:DNA Polymerase theta
D004259:DNA-Directed DNA Polymerase; D009705:Nucleosides; D000097462:DNA Polymerase theta