Abstract
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.
Highlights
External guide sequences (EGSs), transcription activator-like effectors nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPR-associated protein 9 (Cas9) nuclease system potentially function as effective therapeutic approaches to treat brain diseases associated with CMV infections through designing a specific DNA or RNA sequence that target genes required for viral growth
The results indicated that the CRISPR/Cas9 system can be effectively targeted human CMV (HCMV) genomes as a potent prophylactic and therapeutic antiviral agent that may be used to block CMV replication and remove latent viruses
The results suggested that transcription activator-like effector nucleases (TALENs) potentially provided an effective approach to remove latent viruses in animals [86]
Summary
The brain is one’s body control center which controls thoughts, memory, learning, speech, and movement, and regulates many organ functions. Nausea, speech difficulty, ear bleeding, numbness, paralysis, memory loss, concentration problem [1,2]. Depression, anxiety, agitation, delusion, stress, obsession, adaptation difficulty, emotional reaction, odd behavior, retarded intellectual development [3,4]. Apathy, tremor, rigid, unstable posture, speech difficulty, movement retardation, facial nerve paralysis, disorientation, intellectual problem, mood change [5,6]. Seizure, numbness or tingling in arms or legs, nausea, vomiting, personality change, movement difficulty, imbalance, change in hearing, speech or vision [13,14,15]
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