Animal models to study Alzheimer’s disease (AD) pathogenesis are under development. Since herpesviruses have been postulated to be capable of triggering the pathogenic process, AD animal models (mouse, pig, and non-human primates) should be controlled for the presence of these viruses. Only virus-free models allow studying the genetic factors and the effect of adding viruses. Roseoloviruses such as human herpesvirus 6 and the related viruses in the animals are the main topic of this commentary.
BuXL, YaoXQ, JiaoSS, ZengF, LiuYH, XiangY, LiangCR, WangQH, WangX, CaoHY, YiX, DengB, LiuCH, XuJ, ZhangLL, GaoCY1, XuZQ, ZhangM, WangL1, TanXL, XuX, ZhouHD, WangYJ (2015) A study on the association between infectious burden and Alzheimer’s disease. Eur J Neurol22, 1519–1525.
3.
WangY, DingL, ZhuQ, ShuM, CaiQ (2018) Common infections may lead to Alzheimer’s disease. Virol Sin33, 456–458.
4.
ReadheadB, Haure-MirandeJV, FunkCC, RichardsMA, ShannonP, HaroutunianV, SanoM, LiangWS, BeckmannND, PriceND, ReimanEM, SchadtEE, EhrlichME, GandyS, DudleyJT (2018) Multiscale analysis of independent Alzheimer’s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron99, 64–82.e7.
5.
AllnuttMA, JohnsonK, BennettDA, ConnorSM, TroncosoJC, PletnikovaO, AlbertMS, ResnickSM, ScholzSW, De JagerPL, JacobsonS (2020) Human herpesvirus 6 detection in Alzheimer’s disease cases and controls across multiple cohorts. Neuron105, 1027–1035.
6.
BortolottiD, SoffrittiI, D’AccoltiM, GentiliV, Di LucaD, RizzoR, CaselliE (2020) HHV-6A infection of endometrial epithelial cells affects miRNA expression and trophoblast cell attachment. Reprod Sci27, 779–786.
7.
JeongH-H, LiuZ (2019) Are HHV-6A and HHV-7 really more abundant in Alzheimer’s disease?Neuron104, 1034–1035.
8.
ScheurerME, PritchettJC, AmirianES, ZemkeNR, LussoP, LjungmanP (2013) HHV-6 encephalitis in umbilical cord blood transplantation: A systematic review and meta-analysis. Bone Marrow Transplant48, 574–580.
9.
LussoP, CrowleyRW, MalnatiMS, Di SerioC, PonzoniM, BiancottoA, MarkhamPD, GalloRC (2007) Human herpesvirus 6A accelerates AIDS progression in macaques. Proc Natl Acad Sci U S A104, 5067–5072.
10.
LeibovitchE, WohlerJE, Cummings MacriSM, MotanicK, HarbertsE, GaitanMI, MaggiP, EllisM, WestmorelandS, SilvaA, ReichDS, JacobsonS (2013) Novel marmoset (Callithrix jacchus) model of human Herpesvirus 6A and 6B infections: Immunologic, virologic and radiologic characterization. PLoS Pathog9, e1003138.
11.
DennerJ, BigleyTM, PhanTL, ZimmermannC, ZhouX, KauferBB (2019) Comparative analysis of Roseoloviruses in humans, pigs, mice, and other species. Viruses11, 1108.
JakobsenJE, JohansenMG, SchmidtM, Dagnæs-HansenF, DamK, GunnarssonA, LiuY, KraghPM, LiR, HolmIE, CallesenH, MikkelsenJG, NielsenAL, JørgensenAL (2013) Generation of minipigs with targeted transgene insertion by recombinase-mediated cassette exchange (RMCE) and somatic cell nuclear transfer (SCNT). Transgenic Res22, 709–723.
14.
JakobsenJE, JohansenMG, SchmidtM, LiuY, LiR, CallesenH, MelnikovaM, HabekostM, MatroneC, BouterY, BayerTA, NielsenAL, DuthieM, FraserPE, HolmIE, JørgensenAL (2016) Expression of the Alzheimer’s disease mutations AβPP695sw and PSEN1M146I in double-transgenic Göttingen minipigs. J Alzheimers Dis53, 1617–1630.
15.
LeeS-E, HyunH, ParkM-R, ChoiY, SonY-J, ParkYG, JeongS-J, ShinM-Y, HaH-J, HongH-S, ChoiM-K, ImG-S, ParkE-W, Y KimY-H, ParkC, KimE-Y, ParkS-P (2017) Production of transgenic pig as an Alzheimer’s disease model using a multi-cistronic vector system. PLoS One12, e0177933.
16.
CrossSS, ParkerJC, RoweWP, RobbinsML (1979) Biology of mouse thymic virus, a herpesvirus of mice, and the antigenic relationship to mouse cytomegalovirus. Infect Immun26, 1186–1195.
17.
ReynaudJM, HorvatB (2013) Animal models for human herpesvirus 6 infection. Front Microbiol4, 174.