Chlamydia pneumoniae and Herpes Simplex Virus Type 1 Co-infection of Human Astrocytes Alters Host Cell Transcription of β-APP Cleaving Enzyme-1 (BACE1) and Neprilysin, Enzymes Implicated in Alzheimer Disease

Sidra Haque, Danielle Lopez, Syed Jaffrey, Denah Appelt, Susan Hingley

Research output: Contribution to conferencePresentation

Abstract

Chlamydia pneumoniae (Cpn) and herpes simplex virus type 1 (HSV-1) have been studied as pathogens contributing to Alzheimer disease (AD). Since Cpn and HSV1 are both ubiquitous, individuals may be simultaneously colonized with these two pathogens. We speculate that Cpn and HSV-1 act synergistically in promoting AD pathology, specifically processing of amyloid precursor protein (APP). The ability of Cpn and HSV-1 to co-infect astrocytes was visualized by immunofluorescence microscopy (IF) and quantified by RT-PCR. Expression of β-APP cleaving enzyme-1 (BACE1) and neprilysin (NEP), enzymes involved in generating and clearing toxic APP fragments, respectively, were monitored by RT-PCR. IF revealed that a cell could be simultaneously infected with Cpn and HSV-1. Cpn copy numbers derived from co-infected monolayers tended to be slightly greater than that obtained from single infections, indicating that HSV-1 did not prevent Cpn from infecting astrocytes. At early time points, expression of NEP was greatest in co-infected monolayers; by 24 hours post infection (hpi), NEP expression in Cpn-infected monolayers resembled that of co-infected cells and was increased relative to that of uninfected cells, while NEP expression in HSV-1-infected cells was decreased. BACE expression in infected cells was decreased relative to that of uninfected astrocytes through 12 hpi; at 24 hpi, expression in HSV-1- and co-infected monolayers remained decreased while that of Cpn-infected astrocytes resembled that of uninfected cells. BACE expression in Cpn-infected cells was increased relative to that of uninfected cells at 48 hpi. Both IF and RT-PCR data indicate that internalization of Cpn by astrocytes occurs in the presence of HSV-1. Gene expression of BACE1 and NEP varied depending on type of infection suggesting different effects of Cpn and HSV-1 single and dual infections on AD pathology.

Original languageAmerican English
StatePublished - May 8 2019

Keywords

  • Alzheimer disease
  • Chlamydia pneumoniae
  • Herpes simplex virus type 1
  • amyloid precursor protein
  • β-amyloid
  • β-APP cleaving enzyme-1 (BACE1)
  • neprilysin

Disciplines

  • Life Sciences
  • Medicine and Health Sciences

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