Proteomic Characterization of PAMs with PRRSV-ADE Infection.
Viruses
The antibody-dependent enhancement (ADE) effect of a PRRSV infection is that the preexisting sub- or non-neutralizing antibodies specific against PRRSV can facilitate the virus entry and replication, and it is likely to be a great obstacle for the selection of immune strategies and the development of high-efficiency PRRSV vaccines. However, the proteomic characterization of primary alveolar macrophages (PAMs) with a PRRSV-ADE infection has not yet been investigated so far. Therefore, we performed a tandem mass tag (TMT)-based quantitative proteomic analysis of PAMs with a PRRSV-ADE infection in this study. The results showed that a total of 3935 differentially expressed proteins (DEPs) were identified in the PAMs infected with PRRSV-ADE, including 2004 up-regulated proteins and 1931 down-regulated proteins. Further, the bioinformatics analysis for these DEPs revealed that a PRRSV-ADE infection might disturb the functions of ribosome, proteasome and mitochondria. Interestingly, we also found that the expression of the key molecules in the innate immune pathways and antiviral proteins were significantly down-regulated during a PRRSV-ADE infection. This study was the first attempt to analyze the proteomic characterization of PAMs with a PRRSV-ADE infection in vitro. Additionally, the findings will provide valuable information for a better understanding of the mechanism of virus-antibody-host interactions during a PRRSV-ADE infection.
10.3390/v15010036
CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression.
Xu Huiling,Liu Zehui,Zheng Suya,Han Guangwei,He Fang
Vaccines
CD163 has been identified as the essential receptor for Porcine reproductive and respiratory syndrome (PRRSV), a major etiologic agent of pigs. Scavenger receptor cysteine-rich domain 5-9 (SRCR5-9) in CD163 was shown to be responsible for the virus interaction. In this study, monoclonal antibodies (mAbs) 6E8 and 9A10 against SRCR5-9 were selected based on the significant activity to inhibit PRRSV infection in Porcine Alveolar Macrophage (PAMs) and Marc-145. Both mAbs are capable of blocking variable PRRSV strains in a dose-dependent manner. Meanwhile, as candidates for both prevention and therapeutics, the antibodies successfully inhibit PRRSV infection and the related NF-κB pathway either before or after virus attachment. Besides, the antibody treatment with either mAb leads to a remarkable decrease of CD163 transcription in PAMs and Marc-145. It is potentially caused by the excessive accumulation of membrane associated CD163 due to the failure in CD163 cleavage with the antibody binding. Further, conformational epitopes targeted by 6E8 and 9A10 are identified to be spanning residues SXDVGXV in SRCR5 and Q in SRCR7, respectively. CD163 with mutated epitopes expressed in 3D4 cells fails to support PRRSV infection while wild type CD163 recovers PRRSV infection, indicating the critical role of these residues in PRRSV invasion. These findings promote the understanding in the interaction between PRRSV and the receptor and provide novel broad antiviral strategies for PRRSV prevention and treatment via alternative mechanisms.
10.3390/vaccines8040592
Role of CD163 in PRRSV infection.
Virology
Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious agent that poses a significant economic threat to the global swine industry. Efficient viral entry relies on interactions with cellular receptors, with CD163-a cysteine-rich scavenger receptor found on porcine alveolar macrophages (PAMs)-playing a critical role. Extensive evidence supports CD163's essential function in PRRSV infection. This review synthesizes current knowledge about CD163's role, examining its structure-function relationship and identifying specific regions crucial for viral entry. We evaluate the established role of CD163 in PRRSV pathogenesis and highlight areas requiring further investigation, along with the potential for targeted therapeutic interventions. Understanding the molecular determinants of CD163's function is vital for developing effective strategies to control PRRSV infection and mitigate its economic impact on swine production. Further research into the PRRSV-CD163 interactions will be crucial for creating novel antiviral strategies.
10.1016/j.virol.2024.110262
New perspective of host microRNAs in the control of PRRSV infection.
Liu Fang,Du Yinping,Feng Wen-Hai
Veterinary microbiology
Porcine reproductive and respiratory syndrome (PRRS) is one of the most important diseases in pigs, leading to significant economic losses in swine industry worldwide. PRRS virus (PRRSV) is an enveloped positive single-stranded RNA virus, which mainly infects cells of monocyte/macrophage lineage. MicroRNAs (miRNAs) are small non-coding RNAs and have emerged as important regulators of virus-host cell interactions. In the past several years, scientists have been trying to understand the interaction between host miRNAs and PRRSV infection. This review describes the mechanism of host miRNAs modulating the infection and replication of PRRSV, the approaches of delivering miRNAs into hosts, and the transcriptom of host cells during PRRSV infection. miRNAs including miR-181, miR-23, miR-30c, and miR-24-3p are reported to play important roles in PRRSV infection and replication, and in modulating host antiviral responses, while others, for example miR-204, miR-221, miR-219, need more explorations. Importantly, combining with the reverse genetic technique and current miRNAs delivery approaches such as pcDNA, recombinant lentivirus, and exosomes, we propose that miRNAs contribute to and could be used as one of potent factors in controlling PRRSV infection.
10.1016/j.vetmic.2017.01.004
Cellular protein profiles altered by PRRSV infection of porcine monocytes-derived dendritic cells.
Hu Yue,Wu Xiangju,Feng Wenhai,Li Feng,Wang Zhao,Qi Jing,Du Yijun
Veterinary microbiology
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play an important role in inducing primary antigen-specific immune responses. Some viruses have evolved to specifically target DCs to circumvent the host immune responses for their persistence in the host. One example is porcine reproductive and respiratory syndrome virus (PRRSV) that causes a persistent infection in pigs through modulating DC-mediated antiviral response. To study the cellular protein responses in PRRSV-infected monocyte-derived dendritic cells (MoDCs), two-dimensional liquid chromatography-tandem mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling was employed to quantitatively identify the differentially expressed proteins in PRRSV-infected MoDCs and the control cells. A total of 252 cellular proteins in MoDCs that were significantly altered at different time periods post-infection were identified. Differentially expressed proteins that are involved in the endocytosis pathway, actin cytoskeleton network, antigen processing and presentation, JAK-STAT signaling pathway and PRRSV receptors were identified and further analyzed. Among them, the expression changes of STAT1, Mx1, PICALM and SLA-DR were further verified by Western blotting. The protein profiles associated with PRRSV infection of MoDCs should offer novel insights to further investigation of PRRSV-mediated antiviral evasion mechanism and its pathobiology in swine.
10.1016/j.vetmic.2018.11.016
Progress in PRRSV Infection and Adaptive Immune Response Mechanisms.
Viruses
Since its discovery, Porcine reproductive and respiratory syndrome (PRRS) has had a huge impact on the farming industry. The virus that causes PRRS is Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), and because of its genetic diversity and the complexity of the immune response, the eradication of PRRS has been a challenge. To provide scientific references for PRRSV control and vaccine development, this study describes the processes of PRRSV-induced infection and escape, as well as the host adaptive immune response to PRRSV. It also discusses the relationship between PRRSV and the adaptive immune response.
10.3390/v15071442
Mechanism of PRRSV infection and antiviral role of polyphenols.
Virulence
Porcine reproductive and respiratory syndrome (PRRS) is associated with the endemic outbreak of fever, anorexia, and abortion in pregnant sows, resulting in an enormous economic impact on the global swine industry. Current mainstream prophylactic agents and therapies have been developed to prevent PRRSV infection; however, they have limited efficacy. Therefore, there is an urgent need to develop novel antiviral strategies to prevent PRRSV infection and transmission. The identification of new PRRSV entry mediators, such as MYH9 and HSPA8; viral apoptotic mimicry; and TIM-induced macropinocytosis, to facilitate infection has led to a novel molecular understanding of the PRRSV infection mechanism, which can be utilized in the development of prophylactic agents and therapies for PRRSV infection. Polyphenols, complex chemical molecules with abundant biological activities derived from microorganisms and plants, have demonstrated great potential for controlling PRRSV infection via different mechanisms. To explore new possibilities for treating PRRSV infection with polyphenols, this review focuses on summarizing the pathogenesis of PRRSV, reviewing the potential antiviral mechanisms of polyphenols against PRRSV, and addressing the challenges associated with the widespread use of polyphenols.
10.1080/21505594.2024.2417707
Porcine reproductive and respiratory syndrome virus nsp4 positively regulates cellular cholesterol to inhibit type I interferon production.
Ke Wenting,Zhou Yanrong,Lai Yinan,Long Siwen,Fang Liurong,Xiao Shaobo
Redox biology
Cellular cholesterol plays an important role in the life cycles of enveloped viruses. Previous studies by our group and other groups have demonstrated that the depletion of cellular cholesterol by methyl-β-cyclodextrin (MβCD) reduces the proliferation of porcine reproductive and respiratory syndrome virus (PRRSV), a porcine Arterivirus that has been devastating the swine industry worldwide for over two decades. However, how PRRSV infection regulates cholesterol synthesis is not fully understood. In this study, we showed that PRRSV infection upregulated the activity of protein phosphatase 2 (PP2A), which subsequently activated 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in the cholesterol synthesis pathway, to increase the levels of cellular cholesterol. By screening the PRRSV-encoded proteins, we showed that nsp4 dominated the upregulation of cellular cholesterol, independently of the 3C-like protease activity of nsp4. A mutation analysis showed that domain I (amino acids 1-80) of PRRSV nsp4 interacted with PR65 alpha (PR65α), the structural subunit, and PP2Ac, the catalytic subunit, of PP2A. Importantly, domain I of nsp4 inhibited Sendai virus-induced interferon β production, and this inhibitory effect was eliminated by Lovastatin, an HMGCR inhibitor, indicating that the upregulation of cellular cholesterol by nsp4 is a strategy used by PRRSV to suppress the antiviral innate immunity of its host. Collectively, we here demonstrated the mechanism by which PRRSV regulates cellular cholesterol synthesis and reported a novel strategy by which PRRSV evades its host's antiviral innate immune response.
10.1016/j.redox.2021.102207