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Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections

by Shao-Cheng Wang 1,2,†, Shiu-Jau Chen 3,4,† and Yuan-Chuan Chen 5,*
1
Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan 71742, Taiwan
2
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
3
Department of Neurosurgery, Mackay Memorial Hospital, Taipei 10449, Taiwan
4
Department of Medicine, Mackay Medicine College, New Taipei City 25245, Taiwan
5
Program in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(4), 1376; https://doi.org/10.3390/ijms21041376
Received: 24 December 2019 / Revised: 29 January 2020 / Accepted: 15 February 2020 / Published: 18 February 2020
Cytomegalovirus (CMV) is one of the major human health threats worldwide, especially for immunologically comprised patients. CMV may cause opportunistic infections, congenital infections, and brain diseases (e.g., mental retardation and glioblastoma). The etiology of brain diseases associated with human CMV (HCMV) infections is usually complex and it is particularly difficult to treat because HCMV has a life-long infection in its hosts, high mutation rate, and latent infections. Moreover, it is almost impossible to eradicate latent viruses in humans. Although there has been progress in drug discovery recently, current drugs used for treating active CMV infections are still limited in efficacy due to side effects, toxicity, and viral resistance. Fortunately, letermovir which targets the HCMV terminase complex rather than DNA polymerase with fewer adverse reactions has been approved to treat CMV infections in humans. The researchers are focusing on developing approaches against both productive and latent infections of CMV. The gene or RNA targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) are being investigated to remove acute and/or latent CMV infections. For the treatment of glioblastoma, vaccine therapy through targeting specific CMV antigens has improved patients’ survival outcomes significantly and immunotherapy has also emerged as an alternative modality. The advanced research for developing anti-CMV agents and approaches is promising to obtain significant outcomes and expecting to have a great impact on the therapy of brain diseases associated with CMV infections. View Full-Text
Keywords: cytomegalovirus; brain disease; mental retardation; glioblastoma; gene/RNA targeting approach; vaccine therapy; immunotherapy cytomegalovirus; brain disease; mental retardation; glioblastoma; gene/RNA targeting approach; vaccine therapy; immunotherapy
MDPI and ACS Style

Wang, S.-C.; Chen, S.-J.; Chen, Y.-C. Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections. Int. J. Mol. Sci. 2020, 21, 1376.

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