The mutated tegument protein UL7 attenuates the virulence of herpes simplex virus 1 by reducing the modulation of α-4 gene transcription.
UL7, a tegument protein of Herpes Simplex Virus type I (HSV-1), is highly conserved in viral infection and proliferation and has an unknown mechanism of action.



A HSV-1 UL7 mutant (UL7-MU) was constructed using the CRISPR-cas9 system. The replication rate and plaque morphology were used to analyze the biological characteristics of the wild-type (WT), UL7-MU and MU-complemented P1 viruses. The virulence of the viruses was evaluated in mice. Real-time RT-qPCR and ChIP assays were used to determine the expression levels of relevant genes.



The replication capacity of a recombinant virus (UL7-MU strain) was 10-fold lower than that of the WT strain. The neurovirulence and pathologic effect of the UL7-MU strain were attenuated in infected mice compared with the WT strain. In the latency model, the expression of latency-associated transcript (LAT) in the central nervous system (CNS) and trigeminal nerve was lower in UL7-MU-infected mice than in WT strain-infected mice. The transcription level of the immediate-early gene α-4 in UL7-MU-infected cells was reduced by approximately 2-fold compared with the clear transcriptional peak identified in WT strain-infected Vero cells within 7 h post-infection (p.i.).



By modulating the transcription of the α-4 gene, UL7 may be involved in transcriptional regulation through its interaction with the transcript complex structure of the viral genome during HSV-1 infection.
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Xingli
X
Xu
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Shengtao
S
Fan
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Jienan
J
Zhou
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Ying
Y
Zhang
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Yanchun
Y
Che
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Hongzhi
H
Cai
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Lichun
L
Wang
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Lei
L
Guo
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China.
Longding
L
Liu
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, Yunnan, China. liqihan@imbcams.com.cn.
Qihan
Q
Li
D000818:Animals; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
D017874:Immediate-Early Proteins; C000597859:UL7 protein, human herpesvirus 1; D014763:Viral Matrix Proteins; C048925:herpes simplex virus, type 1 protein ICP4
Herpes Simplex Virus type I; Transcription; UL7; α-4 gene