Investigating the expression and role of proliferating cell nuclear antigen in monocytes and macrophages of SIV infected rhesus macaques

Abstract

Proliferating cell nuclear antigen (PCNA) is a DNA polymerase δ auxiliary protein during cell cycle. However, PCNA is also present in quiescent cells undergoing DNA repair. This study investigates the expression of PCNA in CNS macrophages of SIV infected Rhesus macaque and examines the presence of PCNA in monocytes prior to differentiation into CNS macrophages. Accumulation of macrophages in the SIV infected brain, together with the creation of multinucleated giant cells (MNGC), form SIV lesions, which lead to neurological disorders. From the twelve animals used in this study, four were analyzed by flow cytometry to detect PCNA expression in monocytes, but no expression of PCNA was detected. Peripheral blood mononuclear cells (PBMC) of five animals were also analyzed using cytospin preparations to confirm results obtained by flow cytometry. The study did not find induction of PCNA mRNA by qRT-PCR in infected animals. Animals that developed SIVE were analyzed by immunohistochemistry to identify PCNA in recently immigrated macrophages. Together results suggest that 1) PCNA is not expressed in monocytes; 2) PCNA in monocyte/macrophages is induced in SIV infected animals and it is not associated with cell cycle; 3) Recently immigrated monocytes of CNS are PCNA negative and 4) majority PCNA+ macrophages in the SIVE lesions are perivascular macrophages.