Dataset Information

Differential host cell gene expression regulated by the porcine reproductive and respiratory syndrome virus GP4 and GP5 glycoproteins.

ABSTRACT: The porcine reproductive and respiratory syndrome virus (PRRSV) GP4 and GP5 proteins are two membrane-associated viral glycoproteins that have been shown to induce neutralizing antibodies. In the present study, the host cell gene expression profiles altered by the GP4 and GP5 proteins were investigated by the use of DNA microarrays. Sublines of Marc-145 and HeLa cells were established by stable transfection with open reading frame (ORF)4 and ORF5 of PRRSV, respectively, and differential gene expressions were studied using microarray chips embedded with 1718 human-expressed sequence tags. The genes for protein degradation, protein synthesis and transport, and various other biochemical pathways were identified. No genes involved in the apoptosis pathway appeared to be regulated in GP5-expressing cells. The microarray data may provide insights into the specific cellular responses to the GP4 and GP5 proteins during PRRSV infection.

SUBMITTER: Lee C

PROVIDER: S-EPMC7112691 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential host cell gene expression regulated by the porcine reproductive and respiratory syndrome virus GP4 and GP5 glycoproteins.

Lee Changhee C Bachand Aimee A Murtaugh Michael P MP Yoo Dongwan D

Veterinary immunology and immunopathology 20041201 3

The porcine reproductive and respiratory syndrome virus (PRRSV) GP4 and GP5 proteins are two membrane-associated viral glycoproteins that have been shown to induce neutralizing antibodies. In the present study, the host cell gene expression profiles altered by the GP4 and GP5 proteins were investigated by the use of DNA microarrays. Sublines of Marc-145 and HeLa cells were established by stable transfection with open reading frame (ORF)4 and ORF5 of PRRSV, respectively, and differential gene exp ...[more]

PMID: 15507305

Similar Datasets

Project description:Studying viral glycoprotein-host membrane protein interactions contributes to the discovery of novel cell receptors or entry facilitators for viruses. Glycoprotein 5 (GP5), which is a major envelope protein of porcine reproductive and respiratory syndrome virus (PRRSV) virions, is a key target for the control of the virus. Here, the macrophage receptor with collagenous structure (MARCO), which is a member of the scavenger receptor family, was identified as one of the host interactors of GP5 through a DUALmembrane yeast two-hybrid screening. MARCO was specifically expressed on porcine alveolar macrophages (PAMs), and PRRSV infection downregulated MARCO expression both in vitro and in vivo. MARCO was not involved in viral adsorption and internalization processes, indicating that MARCO may not be a PRRSV-entry facilitator. Contrarily, MARCO served as a host restriction factor for PRRSV. The knockdown of MARCO in PAMs enhanced PRRSV proliferation, whereas overexpression suppressed viral proliferation. The N-terminal cytoplasmic region of MARCO was responsible for its inhibitory effect on PRRSV. Further, we found that MARCO was a proapoptotic factor in PRRSV-infected PAMs. MARCO knockdown weakened virus-induced apoptosis, whereas overexpression aggravated apoptosis. MARCO aggravated GP5-induced apoptosis, which may result in its proapoptotic function in PAMs. The interaction between MARCO and GP5 may contribute to the intensified apoptosis induced by GP5. Additionally, the inhibition of apoptosis during PRRSV infection weakened the antiviral function of MARCO, suggesting that MARCO inhibits PRRSV through the regulation of apoptosis. Taken together, the results of this study reveal a novel antiviral mechanism of MARCO and suggest a molecular basis for the potential development of therapeutics against PRRSV. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) has been one of the most serious threats to the global swine industry. Glycoprotein 5 (GP5) exposed on the surface of PRRSV virions is a major glycoprotein, and it is involved in viral entry into host cells. A macrophage receptor with collagenous structure (MARCO), which is a member of the scavenger receptor family, was identified to interact with PRRSV GP5 in a DUALmembrane yeast two-hybrid screening. Further investigation demonstrated that MARCO may not serve as a potential receptor to mediate PRRSV entry. Instead, MARCO was a host restriction factor for the virus, and the N-terminal cytoplasmic region of MARCO was responsible for its anti-PRRSV effect. Mechanistically, MARCO inhibited PRRSV infection through intensifying virus-induced apoptosis in PAMs. The interaction between MARCO and GP5 may contribute to GP5-induced apoptosis. Our work reveals a novel antiviral mechanism of MARCO and advances the development of control strategies for the virus.

Project description:Porcine Reproductive and Respiratory Syndrome (PRRS) is historically the most economically important swine disease worldwide that severely affects the reproductive performance of sows. However, little is still known about the genetic basis of reproductive performance in purebred herds during a PRRS outbreak through the comparison of maternal and terminal breeds. Thus, the objective of this work was to explore the host genetics of response to PRRS in purebred sows from two breeds. Reproductive data included 2546 Duroc and 2522 Landrace litters from 894 and 813 purebred sows, respectively, which had high-density genotype data available (29,799 single nucleotide polymorphisms; SNPs). The data were split into pre-PRRS, PRRS, and post-PRRS phases based on standardized farrow-year-week estimates. Heritability estimates for reproductive traits were low to moderate (≤0.20) for Duroc and Landrace across PRRS phases. On the other hand, genetic correlations of reproductive traits between PRRS phases were overall moderate to high for both breeds. Several associations between MARC0034894, a candidate SNP for response to PRRS, with reproductive performance were identified (P-value < 0.05). Genomic analyses detected few QTL for reproductive performance across all phases, most explaining a small percentage of the additive genetic variance (≤8.2%, averaging 2.1%), indicating that these traits are highly polygenic. None of the identified QTL within a breed and trait overlapped between PRRS phases. Overall, our results indicate that Duroc sows are phenotypically more resilient to PRRS than Landrace sows, with a similar return to PRRS-free performance between breeds for most reproductive traits. Genomic prediction results indicate that genomic selection for improved reproductive performance under a PRRS outbreak is possible, especially in Landrace sows, by training markers using data from PRRS-challenged sows. On the other hand, the high genetic correlations with reproductive traits between PRRS phases suggest that selection for improved reproductive performance in a clean environment could improve performance during PRRS, but with limited efficiency due to their low heritability estimates. Thus, we hypothesize that an indicator trait that could be indirectly selected to increase the response to selection for these traits would be desirable and would also improve the reproductive performance of sows during a PRRS outbreak.

Dataset Information

Differential host cell gene expression regulated by the porcine reproductive and respiratory syndrome virus GP4 and GP5 glycoproteins.

Publications

Differential host cell gene expression regulated by the porcine reproductive and respiratory syndrome virus GP4 and GP5 glycoproteins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets