Cysteine residues of the porcine reproductive and respiratory syndrome virus ORF5a protein are not essential for virus viability

Sun, Lichang; Zhou, Yan; Liu, Runxia; Lǐ, Yànhuá; Gao, Fei; Wang, Xiaomin; Fan, Hongjie; Yuan, Sheng; Wei, Zuzhang; Tong, Guangzhi

doi:10.1016/j.virusres.2014.12.004

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Also, epitopes may be non-contiguous, where antibody molecules bind residues that span different epitopes or even different proteins. Glycoproteins 2, 3 and 4 associate to form trimeric complexes in the viral envelope, which has been shown to interact with E protein, ORF5a protein, and the GP5-M dimer (55, 62). Therefore, the essential features of neutralizing epitopes may bind components of more than one protein in the complex.…”

Section: Discussionmentioning

confidence: 99%

Porcine reproductive and respiratory syndrome virus neutralizing antibodies provide in vivo cross-protection to PRRSV1 and PRRSV2 viral challenge

et al. 2018

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Vaccine control and prevention of porcine reproductive and respiratory syndrome (PRRS), the most important disease of swine, is difficult to achieve. However, the discovery of broadly neutralizing antibody activity against porcine reproductive and respiratory syndrome virus (PRRSV) under typical field conditions opens the door to new immunologic approaches for robust protection. We show here that passive administration of purified immunoglobulins with neutralizing antibodies reduced PRRSV2 infection by up to 96%, and PRRSV1 infection by up to 87%, whereas immune immunoglobulins lacking neutralizing activity had no effect on viral infection. Hence, immune competence of passive immunoglobulin transfer was associated specifically with antibody neutralizing activity. Current models of PRRSV infection implicate a minor envelope glycoprotein (GP) complex including GP2, GP3, and GP4, as critical to permissive cell infection. However, conserved peptides comprising the putative cell attachment structure did not attenuate neutralization or viral infection. The results show that immunological approaches aimed at induction of broadly neutralizing antibodies may substantially enhance immune protection against PRRSV. The findings further show that naturally occurring viral isolates are able to induce protective humoral immunity against unrelated PRRSV challenge, thus removing a major conceptual barrier to vaccine development.

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Section: Discussionmentioning

confidence: 99%

Porcine reproductive and respiratory syndrome virus neutralizing antibodies provide in vivo cross-protection to PRRSV1 and PRRSV2 viral challenge

et al. 2018

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“…Previous reports suggested that ORF5a was essential for virus viability and infectivity [ 17 , 20 ], whereas another study reported that the ORF5a antibody response is neither neutralizing nor protective against PRRSV [ 22 ]. The ORF5a protein possessed two cysteines at positions 29 and 30 that are highly conserved among NA genotype PRRSVs, and a previous study revealed that replacement of cysteine with glycine at position 30 caused the ORF5a protein to interact non-covalently with itself, which may account for the lethal phenotype of mutants carrying substitution of cysteine to glycine at position 30 [ 21 ]. No mutation existed at position 30 in this study (denoted with a red box in Fig.…”

Section: Resultsmentioning

confidence: 99%

Analysis of genetic variation of porcine reproductive and respiratory syndrome virus (PRRSV) isolates in Central China

Liu

Yi-bao

et al. 2016

The Journal of Veterinary Medical Science

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Porcine reproductive and respiratory syndrome virus (PRRSV) is an epidemic etiology in pigs of all ages causing reproductive failure and respiratory manifestation. PRRSV has been circulating in Chinese pig farms for almost 20 years. The aim of the present study was to fully understand the extent of the genetic diversity and molecular characteristics of PRRSVs in Central China. A strain of PRRSV isolated from a recent outbreak farm in Hunan province in Central China, designated HUN-2014, was sequenced and analyzed with 39 other PRRSVs from 1998 to 2014 in Central China. Comparative results of genomic sequences revealed that all 40 PRRSVs belonged to the North American genotype (NA genotype) and shared 88.8–99.0% homology. Phylogenetic analysis showed three subgenotypes, namely conventional PRRSV (C-PRRSV), specially mutant PRRSV (S-PRRSV) and highly pathogenic PRRSV (HP-PRRSV), in all 40 PRRSVs. Moreover, comparative analysis of amino acid (AA) sequences of NSP2, GP3, GP5 and ORF5a revealed the main evolution trend of PRRSVs in Central China from 1998 to 2014, which was from C-PRRSV to HP-PRRSV, accompanied by different evolving directions to S-PRRSV. In conclusion, both the major evolutionary trend and special features of genetic variation should be emphasized as theoretical basis for development of new vaccines and control strategies for PRRS.

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“…PRRSV-2 ORF5a protein contains 2 conserved Cys at position 29 and 30 while PRRSV-1 ORF5a protein contains only one Cys residue at position 30. The protein interacts noncovalently with itself and with the GP4 and E proteins [27]. Both Cys residues in the ORF5a of PRRSV-2 are not essential for virus infectivity [27].…”

Section: Identification Of Essential and Non-essential Viral Genomic mentioning

confidence: 99%

“…The protein interacts noncovalently with itself and with the GP4 and E proteins [27]. Both Cys residues in the ORF5a of PRRSV-2 are not essential for virus infectivity [27]. While the biological functions of the ORF5a protein remain largely unknown, this protein was found to be indispensable for viral infectivity [26].…”

Section: Identification Of Essential and Non-essential Viral Genomic mentioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Virus Reverse Genetics and the Major Applications

Chaudhari

2020

Viruses

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Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or gene fragments, insertion of foreign genes, and swapping genes between PRRSV strains or between PRRSV and other members of the Arteriviridae family. In this review, we describe the approaches to construct an infectious cDNA for PRRSV and the ten major applications of these infectious clones to study virus biology and virus–host interaction, and to design a new generation of vaccines with improved levels of safety and efficacy.

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Cysteine residues of the porcine reproductive and respiratory syndrome virus ORF5a protein are not essential for virus viability

Cited by 5 publications

References 31 publications

Porcine reproductive and respiratory syndrome virus neutralizing antibodies provide in vivo cross-protection to PRRSV1 and PRRSV2 viral challenge

Porcine reproductive and respiratory syndrome virus neutralizing antibodies provide in vivo cross-protection to PRRSV1 and PRRSV2 viral challenge

Analysis of genetic variation of porcine reproductive and respiratory syndrome virus (PRRSV) isolates in Central China

Porcine Reproductive and Respiratory Syndrome Virus Reverse Genetics and the Major Applications

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