This TWiV episode, recorded at the 9th European Congress of Virology in Dubrovnik, features discussions with three prominent European virologists: Stéphane Blanc (plant viruses), Vanda Juranić Lisnić (cytomegalovirus), and Elisabeth Puchhammer-Stöckl (Epstein-Barr virus and Multiple Sclerosis). Stéphane Blanc explains the complex replication and transmission strategies of multipartite plant viruses like nanoviruses and tospoviruses, highlighting their unique multicellular infection dynamics and the unusual genomic segment ratios in populations. Vanda Juranić Lisnić details cytomegalovirus's widespread prevalence, its lifelong latency, evasion of the immune system, and severe consequences in immunocompromised individuals and neonates, also discussing mouse CMV as a model. Elisabeth Puchhammer-Stöckl provides a comprehensive overview of Epstein-Barr virus, its link to infectious mononucleosis, and compelling new evidence, including genetic factors, that strongly associates it with the development of multiple sclerosis through cross-reactive immune responses. The episode collectively offers a diverse snapshot of cutting-edge virology research in Europe.
Virology Throughout Europe: Insights from the European Congress of Virology 2025
0:00 Conference Overview: Hosts Vincent Racaniello and Rich Condit introduce the 9th European Congress of Virology in Dubrovnik, highlighting its collaborative spirit and diverse scientific presentations.
1:39 Guest Introductions: Stéphane Blanc (Plant Health Institute, France), Vanda Juranić Lisnić (University of Rijeka, Croatia), and Elisabeth Puchhammer-Stöckl (Medical University of Vienna, Austria) share their backgrounds and how they entered virology. Elisabeth, originally a physician, emphasizes her patient-centric approach to research.
15:04 Messy Packaging & Multicellular Infection: Tospoviruses exhibit highly variable RNA packaging. Nanoviruses uniquely replicate with different genomic segments in different plant cells, relying on gene product trafficking between cells, making the infectious unit multicellular.
29:28 Unexpected Genome Formulas: In nanoviruses, some segments are up to 20 times more frequent than others, even for essential genes, defying the expectation of equal frequency and suggesting complex regulatory or evolutionary mechanisms.
34:25 Cytomegalovirus (CMV) - A Ubiquitous Herpesvirus: Vanda Juranić Lisnić discusses CMV, a large dsDNA herpesvirus common in humans, establishing lifelong latency and reactivating during immunosuppression.
36:40 Congenital CMV Risks: Primary CMV infection during pregnancy is a major concern, potentially causing severe fetal damage. Despite being a TORCH pathogen, public awareness is low.
42:19 Immune Evasion & "Immune Inflation": CMV causes "immune inflation," where virus-specific T-cells continuously increase, and employs extensive immunoevasion strategies, including manipulating MHC and developing decoy molecules.
44:04 Mouse CMV (MCMV) Model: MCMV is a crucial model due to its close relation to human CMV, despite differences like not passing the placenta. It accurately mimics immune responses and neurological outcomes in infected newborn mice.
50:52 Ovarian Replication & Fertility: MCMV shows high tropism and replication in mouse ovaries (corpus luteum), with implications for human CMV and potential links to ovarian cancer, though fertility impacts are unclear.
56:49 Epstein-Barr Virus (EBV) & MS Link: Elisabeth Puchhammer-Stöckl describes EBV, a highly prevalent herpesvirus often asymptomatic, which can cause infectious mononucleosis.
1:03:56 Strong EBV-MS Association: Recent epidemiological studies strongly link EBV infection to Multiple Sclerosis (MS), an autoimmune disease targeting the CNS. MS patients show higher cross-reactive antibodies against EBV proteins (EBNA381–452) and CNS-derived proteins (GlialCAM, MBP, etc.).
1:11:31 Genetic Predisposition to MS: Specific human HLA-E genetic variants combined with particular EBV LMP1 viral strains significantly increase MS risk (e.g., 260-fold), suggesting a less efficient viral control leads to more autoimmune responses.
1:14:36 MS Prevention & Treatment Prospects: Early detection of consistently high autoantibody levels post-mononucleosis could allow for early intervention with immunosuppressive therapy to delay MS onset.
1:16:45 Vaccine Challenges: Developing EBV and CMV vaccines is challenging due to their complex biology and potential for autoimmune issues, although some progress is being made.