Human cytomegalovirus IE2 may impair the cognitive ability of the hippocampus through the GluNRs/CaMKIIα/CREB signaling pathway in the Rosa26-LSL-IE2/Cre mouse

Behav Brain Res. 2022 Feb 15;419:113683. doi: 10.1016/j.bbr.2021.113683. Epub 2021 Nov 26.


Nowadays, there are few studies in vivo to explore the effects of Human Cytomegalovirus (HCMV) single gene such as immediate early protein 2 (IE2) on the nervous system, let alone the mechanism that IE2 causes cognitive impairment. In this study, the Rosa26-LSL-IE2/Cre mouse was used to show the effects of IE2 on the cognitive ability and the GluNRs/CaMKIIα/CREB signaling pathway in the hippocampus. We divided the mice into experimental and control groups based on the results of PCR firstly. After that, the cognitive abilities of the two groups were compared through new object recognition (NOR) and Morris water maze (MWM) tests. The results of the behavioral tests showed that the cognitive ability of the experimental mice was lower than that of the control group. It is known that changes in the expression levels of N-methyl D-aspartate receptor 1, 2A, and 2B (GluN1, GluN2A, GluN2B) affect synaptic plasticity and cause cognitive changes. Finally, we analyzed the expression levels of GluN1, GluN2A, GluN2B, and related signaling pathway molecules by qPCR and western blot. We found that the expression levels of the GluNRs/CaMKIIα/CREB signaling pathway were decreased in the experimental group. These results indicated that IE2 could affect the expression levels of GluNRs/CaMKIIα/CREB signaling pathway, which was closely related to the cognitive impairment of the experimental group. In summary, we used this novel mouse model to show that IE2 could cause cognitive impairment in the hippocampus, which might be related to the GluNRs/CaMKIIα/CREB signaling pathway. It is helpful to further understand the mechanism of the cognitive impairment induced by HCMV IE2.

Keywords: Cognitive ability; Immediate early protein 2 (IE2); Mouse model; N-methyl D-aspartate receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cognitive Dysfunction / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cytomegalovirus / genetics*
  • Disease Models, Animal
  • Hippocampus / metabolism*
  • Immediate-Early Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Signal Transduction / physiology
  • Viral Proteins / metabolism*


  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Immediate-Early Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Viral Proteins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2