Capsid amino acids at positions 247 and 270 are involved in the virulence of betanodaviruses to European sea bass

European sea bass (Dicentrarchus labrax) is severely afected by nervous necrosis disease, caused by nervous necrosis virus (NNV). Two out of the four genotypes of this virus (red-spotted grouper nervous necrosis virus, RGNNV; and striped jack nervous necrosis virus, SJNNV) have been detected in sea bass, although showing diferent levels of virulence to this fsh species. Thus, sea bass is highly susceptible to RGNNV, whereas outbreaks caused by SJNNV have not been reported in this fsh species. The role of the capsid protein (Cp) amino acids 247 and 270 in the virulence of a RGNNV isolate to sea bass has been evaluated by the generation of recombinant RGNNV viruses harbouring SJNNV-type amino acids in the above mentioned positions (Mut247Dl965, Mut270Dl965 and Mut247+270Dl965). Viral in vitro and in vivo replication, virus virulence and fsh immune response triggered by these viruses have been analysed. Mutated viruses replicated on E-11 cells, although showing some diferences compared to the wild type virus, suggesting that the mutations can afect the viral cell recognition and entry. In vivo, fsh mortality caused by mutated viruses was 75% lower, and viral replication in sea bass brain was altered compared to non-mutated virus. Regarding sea bass immune response, mutated viruses triggered a lower induction of IFN I system and infammatory response-related genes. Furthermore, mutations caused changes in viral serological properties (especially the mutation in amino acid 270), inducing higher seroconversion and changing antigen recognitionThis study has been supported by the projects AGL2017-84644-R (MINECO/AEI/FEDER, UE) and AGL2014-53532-C (MINECO/FEDER). The authors thank Juan Gémez for helping in lab work. P.M. was supported by a Fellowship of the Ministerio de Educación, Spanish Government, and a contract of the project AGL2017-84644-R (MINECO/AEI/FEDER, UE). R.L.-R. was supported by the project P12-RNM-2261 (Junta de Andalucia)S

Patogénesis y profilaxis de la infección por el virus de la enfermedad de linfocistis (LCDV-Sa) en doradas cultivadas (Sparus aurata L.)

Fecha de lectura de Tesis Doctoral: 12 de julio 2019.Los estudios relacionados con la enfermedad de linfocistis (LCD) en dorada (Sparus aurata) se han centrado recientemente en el esclarecimiento de diversos aspectos relacionados con la patogénesis de Lymphocystis disease virus 3 (LCDV-Sa), incluyendo ruta de transmisión, determinación del tropismo tisular y celular del virus o caracterización de la histopatología asociada a la enfermedad. Hay escasos estudios relacionados con la interacción patógeno-hospedador y, además, no existen métodos eficaces para prevenir las infecciones por LCDV-Sa en doradas. Por tanto, en este trabajo se ha profundizado en el estudio de la patogénesis del LCDV-Sa en doradas y en el desarrollo de una vacuna DNA para la prevención de la infección viral. Los resultados nos permiten determinar que la respuesta inmune de doradas frente a una infección por LCDV-Sa está caracterizada por una activación parcial del sistema IFN tipo I, acompañada de una falta de respuesta inflamatoria sistémica, que unido a la activación temprana del gen il10 permite el establecimiento de infecciones asintomáticas persistente. Finalmente, la vacuna DNA desarrollada muestra una distribución sistémica y una correcta expresión, además de aportar una protección impidiendo la multiplicación vírica y/o propiciando la eliminación del virus. Además, se ha demostrado una respuesta inmune humoral en suero a los 3 meses post-vacuación

SARS-CoV-2 variants evolve convergent strategies to remodel the host response

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics