A Recombinant Rabies Virus Chimera Expressing the DC-Targeting Molecular MAB2560 Shows Enhanced Vaccine Immunogenicity Through Activation of Dendritic Cells

 Rabies is an important zoonotic disease caused by the virus from order Mononegavirales, family Rhabdoviridae, rabies virus (RABV). The mortality rate of rabies cases is nearly 100% in animals and humans, making it a serious threat to global health. There is no effective medications or therapies for rabies, and the best method to preventing and controlling the rabies is through vaccination. Recombinant rabies virus, rCVS11-MAB2560 was constructed from RABV CVS11 strain. When used as inactivated vaccine, MAB2560 protein that chimeric expressed on the viral particles will aid in targeting and activating the dendritic cells. The expression of MAB2560 protein was not reducing the expression of G protein, the major immunogen of rabies virus, thus, allowing rCVS11-MAB2560 to retain the natural immunogenicity of RABV. Compared to rCVS11, rCVS11-MAB2560 achieved a higher viral titre in mouse neuroblastoma N2A cells and BSR cells and had a lower pathogenicity in experimental mice. The result suggests that the recombinant rCVS11-MAB2560 can induce immune respond effectively than the parent’s virus in the experimental mice and dogs. The rCVS11-MAB2560 can be a new candidate for inactivated rabies vaccine. A better adjuvant with fewer side effects also should be pursued to increase the immunological efficacy of the vaccines. 

(MA)

Structural insights into viral genome replication by the Severe fever with thrombocytopenia syndrome virus L protein

The large (L) protein of severe fever with thrombocytopenia syndrome virus (SFTSV) plays a key role in catalyzing viral genome replication and transcription. Nonetheless, conformational changes of SFTSV L protein in complex with viral RNA, during viral genome replication and transcription are unclear. Cryo-electron microscopy, in addition to in vitro biochemical and cell-based mini-replicon assays, was used to study structural changes of the SFTSV L-protein during viral genome replication, from pre-initiation to late-stage elongation. The study reveals that the L protein undergoes several conformational changes upon binding 5' RNA in a hook-like conformation. During early-elongation, the 5' and 3' RNA form a distal duplex structure and the template RNA 3' terminus is positioned to feed on the L protein core, particularly in the RNA dependent RNA polymerase active site. The 5' and 3' RNA distal duplex structure however dissolves as the L protein moves from early-elongation to late-stage elongation. The L-protein stalls at different stages of elongation and the L protein core opens to accommodate a 10bp product template duplex. In late-stage elongation, the template duplex splits and moves towards a designated 3' secondary binding site. The template and progeny RNA exit through template and progeny exit channels respectively.

(LML)

Structural insights into viral genome replication by the severe fever with thrombocytopenia syndrome virus L protein

 Severe fever with thrombocytopenia syndrome virus is a new emerging disease that currently endemic in East Asian countries. Cases of transmission of SFTS virus from human to human have made it a new global phenomenon, so proper countermeasures are needed as a prevention measurement. The SFTS replication process involves the role of the L segment which encodes the enzyme RNA dependent RNA polymerase (RdRp). The study demonstrated that L protein initiate the mechanism of SFTS replication. Using in-vitro biochemical and cell-based mini replicon assay, the study reconstructed the 5 different structures of SFTS virus L protein. L protein initiates the replication of SFTS by conformed the viral 5’ into hook-like shape, formed a duplex in the 3’ RNA terminus for initiation in RdRp active site, and accommodates the duplex formation of a 10 bp product template. The duplex of the product afterwards split with the template to the 3’ secondary binding site. The SFTS L protein undergoes additional remodeling and later advances from pre-initiation to the late-stage elongation. The study found a solid basis for future research into issues how the SFTS virus L protein catalyses viral transcription.
(MA)

Intranasal vaccination of hamsters with a Newcastle disease virus vector expressing the S1 subunit protects animals against SARS-CoV-2 disease

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causal agent of coronavirus disease 19 (COVID-19), has caused one of the most devastating pandemics in history. Biosecurity and control techniques offer short-term responses, while successful vaccine development ensures long-term COVID-19 protection. The NDV has been offered as a possible vector for a SARS-CoV-2 vaccination. In mice and hamsters, the NDV vectored vaccine is safe, immunogenic, and protective against SARS-CoV2. The SARS-CoV-2 S1 subunit and RBD antigens are expressed in a number of recombinant NDV-vectored nasal vaccination candidates. Intranasal delivery of rNDV-based vaccine candidates produced high levels of neutralizing antibodies, prevented damage to the lung, and dramatically decreased the viral load in vaccinated animals' respiratory tracts. NDV-based vaccine candidates fully protected animals against the SARS-CoV2 challenge and might be a viable weapon against COVID-19 in human clinical trials.

(MMR)