Journal of Virology

Venezuelan equine encephalitis virus (VEEV) causes encephalitis in humans and equids, and there are no vaccines or therapeutics for humans. In recent years, non-coding RNAs have emerged as critical regulatory factors affecting different cellular pathways. Specifically, long non-coding RNAs (lncRNAs) have been identified as regulators of antiviral pathways; however, their role in VEEV infection ha…

Porcine reproductive and respiratory syndrome (PRRS) is a major economic burden to the global swine industry. Here, we identify the endoplasmic reticulum (ER) translocon component SSR4 as a critical host factor co-opted by PRRSV. We demonstrate that the viral non-structural protein Nsp2 physically interacts with SSR4 via its PLP2 and hypervariable domains and selectively upregulates its expressio…

Alphaherpesvirinae subfamily members are widespread pathogens that cause a range of significant human and animal diseases, from mild mucocutaneous lesions to severe neurological and neonatal infections. Following primary infection of the craniofacial or genital mucosa, lytic replication occurs in epithelial cells, resulting in the production of infectious virus. Virus shed from infected epithelia…

Virus-host interactions govern infection outcomes and viral evolution, but host determinants that enable or restrict viral replication have been difficult to map comprehensively and in the right cellular contexts. Pooled CRISPR perturbation screens now provide scalable, mechanistic entry points into host dependency and restriction landscapes across diverse viruses. Recent extensions, including si…

The neurotropic betacoronavirus porcine hemagglutinating encephalomyelitis virus (PHEV) subverts early innate defenses to establish persistent neuronal infection. We show that PHEV activates RIG-I-MAVS signaling but hijacks this pathway to induce a delayed IRF7-dependent interferon (IFN-I) response (>12 h post-infection), permitting unchecked replication prior to late-phase immunity. Mechanistica…

Porcine epidemic diarrhea virus (PEDV), a highly lethal alpha coronavirus, primarily infects piglet intestines, yet the role of the intestinal homeostasis regulator NEDD4-a HECT-family E3 ubiquitin ligase-in PEDV infection was previously unknown. This study reveals that NEDD4 inhibits PEDV infection by mediating K63-linked ubiquitination of the viral primase NSP8, targeting a conserved lysine (K1…

Decapod iridescent virus 1 (DIV1), the first isolated species of the genus <i>Decapodiridovirus</i> (family <i>Iridoviridae</i>), is a major pathogen threatening farmed decapods, causing large-scale disease outbreaks and high mortality. However, the mechanisms underlying its cellular entry remain poorly understood. In this study, we investigated DIV1 internalization using hematopoietic tissue cel…

Arteriviruses are diverse +ssRNA viruses (<i>Nidovirales</i> Order; <i>Arteriviridae</i> Family) that infect a variety of mammals. Arterivirus infections can manifest in a variety of ways, ranging from viral hemorrhagic fever to persistent sub-clinical infection. A perplexing feature of arterivirus biology is the unusual network of small glycoproteins that decorate the virion surface. How these g…

Human papillomavirus type 16 (HPV16) is the most prevalent carcinogenic HPV type. Many HPV16 sequence variants have been described, some of which cause protein-coding mutations. However, most experiments have characterized the viral proteins encoded by the HPV16 prototype clone, and some researchers have proposed that variants identified in high-grade lesions and cancers may have higher oncogenic…

The spike (S) protein of SARS-CoV-2 is extensively glycosylated, with N-glycosylation sites remaining highly conserved during viral evolution. While inhibiting N-glycosylation has been shown to significantly suppress SARS-CoV-2 infection, the underlying molecular mechanisms remain incompletely characterized. Here, we identify that two N-glycosylation sites, N61 and N343, are critical for spike ma…

The continuous evolution of coronaviruses compromises the efficacy of existing therapeutic antibodies and replication inhibitors, necessitating antiviral strategies that are resilient to viral escape. Distinct from conventional antibody cocktails that remain vulnerable to spike protein mutations, we evaluated a multi-mechanistic therapy targeting three discrete stages of the viral life cycle: rec…

Human seasonal H3N2 influenza A viruses (IAV) are repeatedly transmitted to swine. Modern indoor swine production facilitates close contact between human employees and pigs in their care during certain husbandry events, like weaning, that may increase the chance of interspecies transmission of IAV. This study investigated the effect of matched and mismatched maternal-derived antibodies (MDA) acqu…

Enteroviruses (EVs), encompassing over 200 sero/genotypes, cause diseases ranging from mild illness to severe systemic infections. Galectin-9 (Gal-9) is an immunomodulatory lectin implicated in various viral infections, yet its role in EVs remains unexplored. Here, we identify Gal-9 as a novel host restriction factor against a broad spectrum of EVs, including EV-A71, EV-D68, and Coxsackievirus B2…

Type I interferons (IFNs) are critical for early antiviral defense, yet their role in shaping vaccine-induced immunity remains incompletely understood. Here, we investigated the impact of type I IFN receptor (IFNαβR) deficiency on immune responses to influenza virus infection and vaccination in IFNαβR-deficient (AB6) mice. AB6 mice exhibited profound susceptibility to influenza virus infection, c…

Volume 97, no. 3, e01977-22, 2023, https://doi.org/10.1128/jvi.01977-22. Figure 3A should appear as shown in this correction. Due to an error during figure assembly, the Western blot image in panel A was placed incorrectly. The Co-IP results of exogenous STAT1 with MGF505-7R and STAT2 with MGF505-7R have been corrected. The results and conclusions of the study remain unaffected. We sincerely apol…

The segmented genome of live-attenuated rotavirus (RV) vaccines provides an ideal platform for developing multivalent vaccines against enteric pathogens. Here, we engineered the commercial human RV vaccine strain LLR as a vector to deliver <i>Clostridium perfringens</i> alpha-toxin (CPA), a critical virulence factor associated with gastroenteritis. A screen of four 2A peptide sequences identified…

Interferon-induced transmembrane protein 3 (IFITM3) blocks fusion of many enveloped viruses with endosomes, likely by rigidifying the cell membrane. We and others have previously reported that cyclosporine A (CsA) treatment rescues the ability of the influenza A virus (IAV) to fuse with and infect IFITM3-expressing cells, but the mechanism of such rescue remained controversial. Here, we employed …

Picornaviruses represent a diverse group of plus-stranded RNA viruses, many of which have been linked to severe diseases in both humans and animals. The viral 3C protease is essential for the maturation of viral proteins and the propagation of picornaviruses and, owing to its cleavage activity against multiple host proteins, is associated with the pathogenesis of picornaviruses. The picornaviral …

The isolation of novel adeno-associated virus (AAV) serotypes has led to significant advances in our understanding of parvovirus biology and vector development for gene therapy by identifying isolates with unique cell tropism and increased efficiency of gene transfer to target cells. AAV44.9 is a natural isolate originally found as a contamination of the laboratory stock of SV15 adenovirus. Its s…