Author: Liu, Nan ; Che, Lihe ; Liu, Quan ; Tan, Qianqian ; Xu, Wenbo ; Zhao, Mengru ; Sui, Liyan ; Pan, Mingming ; Song, Zhixia ; Hou, Zhijun ; Zhao, Yinghua ; Wang, Mengmeng ; Jin, Fangyu ; Fang, Shu

ABSTRACT:

The Alongshan virus (ALSV), a newly identified tick-borne segmented flavivirus, can infect humans and cause Alongshan fever, making it imperative to understand its pathogenic mechanisms for the development of effective intervention strategies. Our previous research has established that ALSV exhibits sensitivity to interferon-beta (IFN-β) while having evolved the ability to antagonize downstream antiviral responses induced by type I IFN (IFN-I); however, the specific effects and underlying mechanisms by which ALSV modulates IFN-I production remain poorly understood. In the present study, we demonstrated that ALSV infection significantly suppresses host IFN-I production triggered by poly(I:C), a synthetic analog of viral double-stranded RNA that activates innate immune pathways. To unravel the molecular basis of this suppression, we systematically evaluated the impact of individual ALSV viral proteins on Toll-like receptor-mediated IFN-I production, revealing a complex regulatory network wherein distinct viral proteins target specific signaling molecules: specifically, VP2 and VP3 were found to be responsible for inhibiting RIG-I-mediated IFN-I production, while NSP2 and VP1b were identified as key inhibitors of MDA5-mediated IFN-I production, highlighting the virus’s strategy of employing multiple proteins to disrupt innate immune signaling. Focusing further on the viral nucleoprotein VP2, we determined that it acts at the upstream signaling level of TANK-binding kinase 1, a critical kinase in the IFN-I signaling cascade. Mechanistically, VP2 directly interacts with RIG-I and mediates its degradation through an autophagy-dependent pathway, thereby impairing the host’s ability to detect viral RNA and initiate IFN-I production. These findings not only expand our understanding of the immune evasion mechanisms employed by novel segmented flaviviruses but also offer valuable insights that could facilitate the development of new preventive and therapeutic strategies for the ALSV infection.

IMPORTANCE:

Alongshan virus (ALSV) is an emerging segmented flavivirus that poses a growing threat to human and animal health across Eurasia. Despite its demonstrated capacity to infect humans and suppress interferon (IFN)-mediated antiviral responses, the precise mechanisms of ALSV immune evasion remain largely undefined. This study identifies the viral nucleoprotein VP2 as a key antagonist of host type I IFN (IFN-I) production. By directly interacting with and promoting the autophagy-mediated degradation of RIG-I, VP2 effectively disrupts innate immune recognition and signaling. This finding not only elucidates a previously unknown mechanism of immune suppression by ALSV but also highlights the virus’s sophisticated strategy of using multiple proteins to selectively target RIG-I and MDA5 pathways. These insights advance our understanding of segmented flavivirus-host interactions and suggest that restoring RIG-I function may be a promising therapeutic strategy against ALSV infection.

01 Oct 2025·VACCINE

Immunogenicity and protection against infectious bursal disease via a transgenic Eimeria acervulina expressing IBDV VP2-2C3d fusion protein

Article

Author: Tang, Xinming ; Yin, Guangwen ; Sun, Yingying ; Suo, Xun ; Liu, Yuehui ; Zhang, Sixin ; Guo, Qingbin ; Liu, Xianyong ; Suo, Jingxia ; Wang, Haodi

Infectious bursal disease (IBD), caused by the infectious bursal disease virus (IBDV), significantly threatens global poultry health by inducing immunosuppression and causing economic losses. To enhance vaccination efficacy, we engineered a transgenic strain of Eimeria acervulina (Ea-2C3d) expressing a fusion protein composed of IBDV VP2 and three tandem C3d segments (3C3d), utilizing C3d's adjuvant properties to boost immune responses. The transgene was generated by integrating codon-optimized VP2 and 3C3d sequences into the E. acervulina genome using restriction enzyme-mediated transfection. PCR, protein, and genome sequencing confirmed the successful integration and expression of VP2 fusion C3d, but only two copies of C3d were successfully expressed, due to a partial deletion of one C3d copy during the transfection process. In vivo studies demonstrated that Ea-2C3d elicited significantly higher anti-VP2 antibody titers than the parental Ea-VP2 strain (P < 0.05), especially following second immunization. Upon challenge with virulent IBDV, chickens immunized with Ea-2C3d displayed reduced bursal lesions (histopathological score ≤ 1) and maintained bursal integrity (bursal index >0.7), comparable to those receiving a commercial subunit vaccine. Despite reduced reproductive capacity in the transgenic parasites, Ea-2C3d maintained its immunogenicity and safety. These findings highlight that C3d adjuvant enhances VP2-mediated protection in a coccidial vector, presenting a novel dual-protection strategy against IBD and coccidiosis.

01 Oct 2025·VETERINARY RESEARCH COMMUNICATIONS

Engineering a recombinant VP2-Based neutralizing epitope vaccine candidate against canine parvovirus: a preliminary immunogenicity assessment

Article

Author: Jin, Yuhan ; Gao, Rui ; Yan, Min ; Zhu, Shengrui ; Ren, Zeheng ; Li, Xinyu ; Bai, Lin ; Wu, Qing ; Shi, Chunxu ; Li, Zhitong ; Guan, Wenpeng ; Ren, Guiping ; Han, Jiachi ; Cao, Weiyue ; Shen, Xinyuan

BACKGROUND:

Canine parvovirus (CPV) poses a severe threat to canine health, necessitating the development of safer and more effective vaccines. While traditional vaccines carry risks of virulence reversion and environmental contamination, subunit vaccines-especially neutralizing epitope vaccines-offer promising alternatives by eliciting targeted immune responses with enhanced safety.

METHODS:

We employed bacterial display technology to express 11 overlapping CPV VP2 gene fragments on the periplasmic membrane of E. coli. Key neutralizing antigenic epitopes of CPV VP2 were mapped using four neutralizing single-chain antibodies in combination with FCM. The identified epitopes were concatenated via GS linkers and expressed as a recombinant VP2D protein. Then, animal experiments were conducted to evaluate the immunogenicity of the epitope-based vaccine in mice.

RESULTS:

The data shows that the antigenic epitopes of the four single-chain antibodies are located in V2-V3, V8, V10 and V11 respectively. After linking five antigenic epitope fragments, we constructed a novel chimeric antigen protein, VP2D, and achieved the efficient expression of VP2D. Animal immunization evaluation results demonstrated that the VP2D vaccine exhibited superior immunological properties compared to both the VP2 vaccine and the commercial vaccine. The VP2D vaccine significantly enhanced the host's capacity to mount both humoral and cellular immune responses. Notably, the antibody titers in the VP2D vaccine group were consistently 1.2- to 1.5-fold higher than those in the VP2 vaccine group throughout the experimental period. Furthermore, the proportions of CD4⁺ T cells and F4/80⁺ cells were increased by up to 12% and 8%, respectively, in the VP2D group. Additionally, both the protein levels and mRNA transcription of inflammatory cytokines were elevated in the VP2D vaccine group relative to both the VP2 and commercial vaccine groups, indicating a consistently enhanced inflammatory response.

CONCLUSIONS:

Identified CPV-VP2 neutralizing antigenic epitopes (70-150, 410-440, 510-585 aa), and an effective candidate vaccine for the prevention of CPV was provided.

News (Medical) associated with VP-2 (Tsinghua University)

19 Jul 2023

·www.prnewswire.com

VARON Launches the Game-changer in the Field--New VP Series Portable Oxygen Concentrator with Increased Mobility and Convenience

SEATTLE, July 19, 2023 /PRNewswire/ -- VARON, a leading oxygen concentrator manufacturer, is proud to announce the launch of a new member of the VP series -- VP-2. This portable oxygen concentrator incorporates innovative technology and advanced features, aiming to provide efficient and reliable oxygen therapy to patients in need wherever they go. Established in 2021, VARON is committed to improving the living quality of people who suffer from pulmonary diseases and addressing the growing demand for reliable and efficient oxygen delivery systems. The company has met rapid growth over the past few years. In 2022, VARON hit a milestone of over 50 thousand units sold, with a 40% increase in annual sales. It now has multiple product series to meet various needs for supplemental oxygen and several warehouses in Europe and America for faster delivery. VARON has extensive experience with respiratory supporting solutions and has developed many remarkable products. The heavy investment in research and development ensures that VARON oxygen concentrators are of the highest quality. As the latest addition to the company's impressive product line, VP-2 has user-friendly controls for easy operation. Although with the replaceable battery, its body is still lighter and more compact than its predecessor VP-1, making it more suitable for outdoor use. But what sets it apart from other products on the market is its Dual Oxygen Supply Mode--In addition to traditional pulse flow oxygen supply, when no inhalation is detected, it automatically releases oxygen every 3 seconds. This Feature effectively solves the problem that normal pulse flow mode sometimes cannot sense gentle or shallow breathing during sleep or due to certain pulmonary diseases. "We are more excited than anyone to introduce the new product to the market," said Darren Wang, CEO of VARON. "Our goal is to make oxygen therapy more accessible by providing reliable, efficient, and affordable solutions for anyone in need. With VP-2 coming out, we believe we are much closer to the goal." Medical professionals and institutions also expressed enthusiasm for the new VARON oxygen concentrator. The previous products have built a good reputation among healthcare providers as the advanced technology and great price make them invaluable tools for healthcare. And many customers know about VARON oxygen concentrators through the recommendation of their healthcare providers. VARON has received wide recognition from its customers for the excellent performance and affordable price of its products. The customer service supervisor of VARON said that they often get feedback from their customers saying that choosing VARON oxygen concentrator is a good investment because compared to many other brands on the market, VARON Oxygen concentrators offer more at an unmatched price. So they are more than excited to know about this new product we are launching. About VARON As one of the leading new forces in oxygen concentrators, VARON has built a good reputation for high-standard products and services. It has always been its commitment to providing exceptional customer support and products. You can reach them through various channels, including phone, live chat, and Email. With a dedicated customer service team, a broad network of authorized distributors worldwide, and extensive resources on their website, you are guaranteed easy access to assistance and maintenance and have a wonderful experience with their products and services. It has always been VARON's pursuit to ensure that convenient and efficient oxygen therapy can be available to all healthcare providers and patients in need worldwide. And they want more people to join them in the cause of addressing respiratory problems and raising public awareness of pulmonary health. Pre-sale/Cooperation Email: [email protected] Whatsapp:+1 2133706080 VARON Website: SOURCE Varon oxygen concentrator

100 Deals associated with VP-2 (Tsinghua University)

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Myeloma	Preclinical	China	Tsinghua University	22 Jul 2019

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