Ziding Yu

Viral infectious diseases pose serious threats to global public health. Host non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, circRNAs, and vtRNAs, act as master regulators of host antiviral defense and viral replication. Current studies on ncRNA-virus interactions are generally fragmented, and most reviews focus on a single virus or a single class of ncRNAs, without combining ncRNA expression dynamics with their biological functions for systematic collation. Herein, we establish a novel four-category classification framework based on ncRNA expression patterns and functional characteristics upon viral infection. To counteract viral infections, the host dynamically modulates the expression of distinct ncRNAs to target proviral host factors, host restriction factors, other ncRNAs, micropeptides, and lipids, thereby orchestrating antiviral innate immune signaling pathways, viral replication cycles, autophagy, apoptosis, metabolic reprogramming, and stress granule formation to establish a multilayered antiviral defense system. Concurrently, representative viruses posing severe threats to global public health, including IAV, DENV, HCV, ZIKV, HIV-1, and SARS-CoV-2, have evolved sophisticated strategies to hijack host ncRNA networks and antagonize host antiviral defenses. This review systematically summarizes and elaborates the conserved regulatory principles of various ncRNAs in the host antiviral response, clarifies the molecular mechanisms by which viruses hijack and antagonize host ncRNAs, further refines the theoretical framework of host ncRNA-virus interactions centered on viral replication regulation, discusses the future research directions under this system, and thus provides a theoretical basis for the development of host ncRNA-based antiviral drugs.

Porcine circovirus (PCV), particularly PCV type 2 (PCV2), is a major pathogen driving porcine circovirus-associated diseases (PCVAD), causing significant economic losses in the swine industry. Accumulating evidence highlights autophagy as a critical host-pathogen interface during PCV infection. PCV2 activates autophagy through reactive oxygen species (ROS)-mediated signaling and metabolic regulators like the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) axis, creating a conducive environment for viral persistence. Concurrently, this virus exploits ubiquitin ligases to induce ubiquitination of cellular immune factors, promoting selective autophagy for immune evasion. Host factors, such as retinol-binding protein 4 (RBP4), act as restriction factors by counteracting viral strategies through autophagy modulation. Environmental stressors could exacerbate PCV2 pathogenesis by amplifying ROS-dependent autophagy, while interventions like taurine mitigate viral replication via ROS/AMPK/mTOR pathway inhibition. This mini-review synthesizes current understandings of PCV-autophagy crosstalk, emphasizing its critical role as a host vulnerability and therapeutic target. Understanding the intricate interplay between autophagy and PCV infection may unveil novel therapeutic targets, such as autophagy modulators, to mitigate viral replication and immune pathology.

The pseudorabies virus (PRV), also known as suid alphaherpesvirus 1 (SuAHV-1), has garnered significant attention due to its broad host range and the economic losses it incurs in the swine industry. This review aims to provide a comprehensive understanding of the intricate virus–host interactions during PRV infection, focusing on the evasion strategies of the virus against the host responses. We also summarize the mechanisms by which PRV manipulates the host cell machinery to facilitate its replication and spread, while simultaneously evading detection and clearance by the immune system. Furthermore, we discuss the latest advancements, such as metabolic, autophagic, and apoptotic pathways in studying these interactions, highlighting the role of various cellular factors and pathways in elucidating virus–host dynamics. By integrating these insights, the article aims to provide a comprehensive overview of the molecular mechanisms underlying PRV pathogenesis and host response, paving the way for the development of novel therapeutic strategies against this virus.

Goose astrovirus (GoAstV) has frequently been isolated in China since it was first identified as the etiological agent of visceral gout in goslings in 2017. However, the actual prevalence of GoAstV infection and its economic impact on commercial goose production remain poorly characterized. Here, virus detection and serological testing were conducted to determine the extent of GoAstV infection in commercial goose flocks. We detected GoAstV RNA in 2 (6/300) of dead-in-shell embryos and day-old hatched goslings by RT-PCR, indicating vertical transmission under natural conditions. Using a virus neutralization test, GoAstV antibodies were detected in 41.761.1 of serum samples from four commercial goose flocks, indicating that infections were common. To determine the virus types circulating in the commercial flocks, we isolated 15 GoAstVs from goose tissue samples from farms located in five provinces during 20182022. Genomic sequence analysis showed that all sequences were corresponded to GoAstV group 2 (GoAstV-2) but were assigned into three capsid subgroups based on sequence variations in the capsid protein. Representative isolates of capsid subgroups were also antigenically evaluated using cross-neutralization tests in LMH cell cultures. The antigenic relatedness values (R) calculated using the Horsfall formula were between 62 and 86, indicating that no significant antigenic differences exist between the isolates. Our findings indicate that GoAstV-2 viruses are an important cause of fatal gout in goose flocks, as well as hatchery contamination in China.

Tembusu virus (TMUV) associated disease is a growing cause of egg production decrease and encephalitis in domestic waterfowl, with expanding distribution. In previous studies, TMUV isolates were phylogenetically classified into two genetic lineages and different clusters with varied pathogenicity. However, little is known about the phenotypic and virulence characteristics of cluster 3 isolates within the duck TMUV lineage. In this study, the etiological agent causing egg drop in a laying chicken farm in southern China was investigated and a TMUV was isolated from pooled tissue samples. Genome sequencing and phylogenetic analysis grouped the isolate into TMUV cluster 3 with closest relation to the mosquito‐origin TMUV YN12193. Cross‐neutralization testing using convalescent sera revealed significant antigenic variation between the isolate and a representative strain of cluster 2.2. The experimental infection of SPF hens confirmed the ability of the isolate to replicate in multiple tissues and led to ovary damage. Additionally, high seroconversion rates (95.83%–100%) were detected in the three flocks following retrospective investigation. Our study demonstrates the occurrence of cluster 3 TMUV infection in laying chickens and that the virus exhibits significant antigenic variation compared with cluster 2 TMUV.

Tembusu virus (TMUV), a highly infectious pathogenic flavivirus, causes severe egg-drop and encephalitis in domestic waterfowl, while the determinants responsible for viral pathogenicity are largely unknown. In our previous studies, virulent strain JXSP_2-4 had been completely attenuated by successive passages in BHK-21 cells and the avirulent strain was designated as JXSP-310. Based on the backbone of JXSP_2-4, a series of chimeric viruses were generated according to the amino acid substitutions in NS5 and their infectivities were also analyzed in cell cultures and ducklings. The results showed that the viral titers of RNA-dependent RNA polymerase (RdRp) domain-swapped cheimeric mutant (JXSP-310^RdRp) in cells and ducklings were both markedly decreased compared with JXSP_2-4, indicating that mutations in the RdRp domain affected viral replication. There are R543K and V711A two amino acid substitutions in the RdRp domain. Further site-directed mutagenesis showed that single-point R543K mutant (JXSP-R543K) exhibited similar replication efficacy compared with JXSP_2-4 in cells, but the viral loads in JXSP-R543K-infected ducklings were significantly lower than that of JXSP_2-4 and higher than JXSP-310^RdRp. Surprisingly, the single-point V711A mutation we introduced rapidly reverted. In addition, qRT-PCR and Western blot confirmed that the mutations in the RdRp domain significantly affected the replication of the virus. Taken together, these results show that R543K substitution in the RdRp domain impairs the in vivo growth of TMUV, but sustaining its attenuated infectivity requires the concurrent presence of the V711A mutation.