Epstein‐Barr virus (EBV) asymptomatically infects over 95% of the global population, and poses a great threat to human health. This review summarizes the complex mechanisms underlying EBV latency programs and their roles in both viral persistence and disease development. We comprehensively analyze the four distinct latency programs (0, I, II, and III) and their associated gene expression patterns, with particular emphasis on the key viral proteins, the Epstein‐Barr virus nuclear antigen EBNA1, EBNA2, EBNA3A/B/C, LMP1, and LMP2A/B. The review explores how these latency programs contribute to various EBV‐associated malignancies and autoimmune conditions, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and multiple sclerosis. We detail the multilayered regulation of EBV latency, encompassing epigenetic modifications, chromatin organization, and long‐range genomic interactions. Recent advances in understanding the molecular mechanisms of EBV latency maintenance and the virus's interaction with host cellular machinery provide new insights into potential therapeutic approaches for EBV‐associated diseases.

The complete mitochondrial DNA sequence of Triplophysa venusta was determined using a PCR-based method in our present study. The genome is totally 16 574 bp in length and contains 13 protein-coding genes, 2 ribosomal RNA, 22 transfer RNA genes, and 1 non-coding control region. The overall base composition of T. venusta is A 27.8%, T 26.9%, C 26.9%, and G 18.4%, with an A + T bias of 54.7%. This complete mitogenome of T. venusta provides a basic data for studies on species identification, molecular systematics, and conservation genetics. The phylogenetic trees consistently showed that the Family Cobitidae was divided into three major clades: the subfamily Botiidae, the subfamily Nemaeheilidae, and the subfamily Cobitinae. Cobitinae and Nomaeheilidae formed a main Loach clade, with Botiidae clustered at the basal.

The Epstein–Barr virus (EBV) nuclear antigen leader protein (EBNALP) is essential for the immortalization of naive B lymphocytes (NBLs). However, the mechanisms remain elusive. To understand EBNALP’s role in B-cell transformation, we compare NBLs infected with wild-type EBV and an EBNALP-null mutant EBV using multi-omics techniques. EBNALP inactivation alters enhancer–promoter interactions, resulting in decreased CCND2 and increased CASP1 and BCL2L11 expression. Mechanistically, EBNALP interacts with and colocalizes with the looping factor YY1. Depletion of EBNALP reduces YY1 DNA-binding and enhancer–promoter interactions, similar to effects observed with YY1 depletion. Furthermore, EBNALP colocalizes with DPF2, a protein that binds to H3K14ac and H4K16ac. CRISPR depletion of DPF2 reduces both EBNALP and YY1 DNA binding, suggesting that the DPF2/EBNALP complex may tether YY1 to DNA to increase enhancer–promoter interactions. EBNALP inactivation also increases enhancer–promoter interactions at the CASP1 and BCL2L11 loci, along with elevated DPF2 and YY1 binding and DNA accessibility. Our data suggest that EBNALP regulates YY1 to rewire the host genome, which might facilitate naive B-cell transformation.

SUMMARY: Epstein-Barr virus (EBV) infects 90% of the population worldwide and is associated with multiple malignancies, including Burkitt, Hodgkin and post-transplant lymphomas, nasopharyngeal and gastric carcinoma. EBV also triggers autoimmune diseases, including multiple sclerosis and systemic lupus erythematosus. While host factors important for EBV B-cell entry have been defined, including CD21/CR2, MHC class II and R9AP, much remains to be learned about host factors that support post-entry steps of EBV infection. To gain insight, we conducted a human genome-wide CRISPR-Cas9 screen. In addition to known EBV B cell receptors/co-receptors, we identified multiple new factors and pathways essential for EBV B cell infection. These included multiple B cell signaling pathways, actin cytoskeleton and nuclear import factors. Knockout of CD19, its tetraspanin chaperone CD81 or karyopherin subunit alpha 1 (KPNA1, also called importin-α5) significantly impaired establishment of EBV infection. EBV and CD19 co-localized at early stages of EBV infection, and the CD19 cytoplasmic tail was important for EBV infection, suggesting CD19 signaling supports EBV uptake. Depletion of KPNA1 significantly impaired establishment of EBV infection, but did not impair production of infectious EBV upon reactivation of latently infected B cells. Together, these results provide insights into pathways that support EBV B cell infection and identify potential therapeutic targets. Importance: EBV infects ∼90% of humans and causes multiple cancers (Burkitt, Hodgkin, post-transplant lymphomas, nasopharyngeal and gastric carcinoma) and autoimmune diseases (MS, lupus). Yet while B cell entry receptors (CD21/CR2, MHC-II, R9AP) were known, the host machinery needed after entry — for the virus to actually establish infection was largely uncharacterized. This study fills that gap. Using CRISPR-Cas9 screening across the whole genome (rather than testing candidate genes), the study uncovered entire pathways B-cell signaling, actin cytoskeleton remodeling, and nuclear import as essential for infection, expanding the known host-dependency landscape well beyond entry receptors. Because these are discrete, druggable host factors tied to a specific stage of infection (establishment, not maintenance or reactivation), they represent candidate targets for preventing EBV-driven malignancies and autoimmune disease potentially more tractable than targeting the virus itself. The work moves EBV research beyond entry receptors to define the post-entry host dependencies that let the virus successfully infect B cells, identifying CD19 signaling and KPNA1-mediated nuclear import as new, targetable choke points relevant to EBV-associated cancers and autoimmunity.