A Nectin1 Mutant Mouse Model Is Resistant to Pseudorabies Virus Infection

Yang, Xiaohui; Yu, Chuanzhao; Zhang, Qiuyan; Hong, Linjun; Gu, Tao; Zheng, Enqin; Xu, Zheng; Li, Zicong; Song, Changxu; Cai, Guangyan; Wu, Zhenfang; Yang, Huaqiang

doi:10.3390/v14050874

Cited by 3 publications

(3 citation statements)

References 41 publications

(61 reference statements)

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“…Recently, Yang et al . generated mice with the F129A mutation in nectin-1 as in our study, infected them with PRV via the subcutaneous route, and showed that the mortality rate and viral loading was decreased in the mutant mice [ 40 ]. The results of our study essentially support their findings.…”

Section: Discussionmentioning

confidence: 99%

Single amino acid mutation of nectin-1 provides remarkable resistance against lethal pseudorabies virus infection in mice

TOMIOKA,

TAKEDA,

OZAKI

et al. 2024

The Journal of Veterinary Medical Science

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An approach to genetically engineered resistance to pseudorabies virus (PRV) infection was examined by using a mouse model with defined point mutation in primary receptor for alphaherpesviruses, nectin-1, by the CRISPR/Cas9 system. It has become clear that phenylalanine at position 129 of nectin-1 is important for binding to viral glycoprotein D (gD), and mutation of phenylalanine 129 to alanine (F129A) prevents nectin-1 binding to gD and virus entry in vitro . Here, to assess the antiviral potential of the single amino acid mutation of nectin-1, F129A, in vivo , we generated genome-edited mutant mouse lines; F129A and 135 knockout (KO). The latter, 135 KO used as a nectin-1 knockout line for comparison, expresses a carboxy-terminal deleted polypeptide consisting of 135 amino acids without phenylalanine 129. In the challenge with 10 LD 50 PRV via intranasal route, perfect protection of disease onset was induced by expression of the mutation of nectin-1, F129A (survival rate: 100% in F129A and 135 KO versus 0% in wild type mice). Neither viral DNA/antigens nor pathological changes were detected in F129A, suggesting that viral entry was prevented at the primary site in natural infection. In the challenge with 50 LD 50 PRV, lower but still strong protective effect against disease onset was observed (survival rate: 57% in F129A and 75% in 135 KO versus 0% in wild type mice). The present results indicate that single amino acid mutation of nectin-1 F129A provides significant resistance against lethal pseudorabies.

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Section: Discussionmentioning

confidence: 99%

Single amino acid mutation of nectin-1 provides remarkable resistance against lethal pseudorabies virus infection in mice

TOMIOKA,

TAKEDA,

OZAKI

et al. 2024

The Journal of Veterinary Medical Science

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show abstract

“…In vivo, homozygous mutant mice with a single point amino acid mutation (F129A) in nectin-1 had milder symptoms and lower mortality than a heterozygous mutant and wild-type mice artificially infected with a highly pathogenic PrV strain. However, the homozygous mutant mice had deficient eye development [ 157 ]. According to the above results, using nectin-1 to establish animals resistant to PrV is a practical approach, although more studies are needed to determine the appropriate mutagenesis mode.…”

Section: Discussionmentioning

confidence: 99%

Membrane fusion, potential threats, and natural antiviral drugs of pseudorabies virus

Feng

et al. 2023

Vet Res

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Pseudorabies virus (PrV) can infect several animals and causes severe economic losses in the swine industry. Recently, human encephalitis or endophthalmitis caused by PrV infection has been frequently reported in China. Thus, PrV can infect animals and is becoming a potential threat to human health. Although vaccines and drugs are the main strategies to prevent and treat PrV outbreaks, there is no specific drug, and the emergence of new PrV variants has reduced the effectiveness of classical vaccines. Therefore, it is challenging to eradicate PrV. In the present review, the membrane fusion process of PrV entering target cells, which is conducive to revealing new therapeutic and vaccine strategies for PrV, is presented and discussed. The current and potential PrV pathways of infection in humans are analyzed, and it is hypothesized that PrV may become a zoonotic agent. The efficacy of chemically synthesized drugs for treating PrV infections in animals and humans is unsatisfactory. In contrast, multiple extracts of traditional Chinese medicine (TCM) have shown anti-PRV activity, exerting its effects in different phases of the PrV life-cycle and suggesting that TCM compounds may have great potential against PrV. Overall, this review provides insights into developing effective anti-PrV drugs and emphasizes that human PrV infection should receive more attention.

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“…Moreover, nectin-1 mutant (F129A) mice presented milder clinical symptoms, decreased viral loads in tissue samples, and lower mortality rates when infected with PRV ( 16 ). Additionally, transgenic mice expressing soluble form of porcine nectin-1 protein were resistant to PRV infection ( 15 ).…”

Section: Cellular Factors Facilitating Prv Attachment and Entrymentioning

confidence: 99%

Host cellular factors involved in pseudorabies virus attachment and entry: a mini review

Tan,

Wang,

Bai

et al. 2023

Front. Vet. Sci.

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Pseudorabies virus (PRV) belongs to the Alphaherpesvirinae subfamily and serves as an exceptional animal model for investigating the infection mechanism of Herpes simplex virus type 1. Notably, PRV has the capability to infect a wide range of mammals, including humans, highlighting its potential as an overlooked zoonotic pathogen. The attachment and entry steps of PRV into host cells are crucial to accomplish its life cycle, which involve numerous cellular factors. In this mini review, we offer a comprehensive summary of current researches pertaining to the role of cellular factors in PRV attachment and entry stages, with the overarching goal of advancing the development of novel antiviral agents against this pathogen.

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A Nectin1 Mutant Mouse Model Is Resistant to Pseudorabies Virus Infection

Cited by 3 publications

References 41 publications

Single amino acid mutation of nectin-1 provides remarkable resistance against lethal pseudorabies virus infection in mice

Single amino acid mutation of nectin-1 provides remarkable resistance against lethal pseudorabies virus infection in mice

Membrane fusion, potential threats, and natural antiviral drugs of pseudorabies virus

Host cellular factors involved in pseudorabies virus attachment and entry: a mini review

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