[Viruses to rescue health: Vaccination]. / Les virus au service de la santé : la vaccination.

Viruses have been used as tools to prevent viral infections themselves for more than two centuries with impressive success. After the empirical discoveries of the first vaccines, today the development of genetic engineering, molecular virology, reverse genetics, the manipulation of viral genomes, their high-throughput sequencing and their chemical synthesis, the mastery of cell culture and purification methods have greatly benefited the development of viral vaccines. Since smallpox and rabies, the history of vaccinology has followed in the footsteps of the history of virology. New mRNA or viral vector vaccines have emerged in recent years. They were developed and distributed to the population in record time in the face of the Covid pandemic. Viruses in the service of health have a bright future ahead of them, whether to prevent other pandemics, to treat cancer, or to finally control HIV and malaria.

Title: Les virus au service de la santé : la vaccination. Abstract: Depuis plus de deux siècles, les virus sont utilisés, avec un succès impressionnant, comme outils de prévention des infections virales. Depuis la variole et la rage, l'histoire de la vaccinologie a suivi les pas de l'histoire de la virologie. Après les découvertes empiriques des premiers vaccins, le développement du génie génétique, de la virologie moléculaire, de la génétique inverse, la manipulation des génomes viraux, leur séquençage à haut débit et leur synthèse chimique, la maîtrise de la culture cellulaire et des méthodes de purification, ont considérablement contribué au développement de nouveaux vaccins viraux. Des vaccins à ARN messager ou à vecteur viral ont ainsi vu le jour ces dernières années et, face à la pandémie de Covid-19, ont été développés et distribués à la population en un temps record. Les virus au service de la santé ont un bel avenir devant eux, que cela soit pour prévenir d'autres pandémies, pour traiter le cancer, ou contrôler, enfin, le VIH ou le Plasmodium, l'agent du paludisme.

Discovery of Genes that Modulate Flavivirus Replication in an Interferon-Dependent Manner.

Establishment of the interferon (IFN)-mediated antiviral state provides a crucial initial line of defense against viral infection. Numerous genes that contribute to this antiviral state remain to be identified. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting 386 individual curated human genes in stimulated microglial cells infected with Zika virus (ZIKV), an emerging RNA virus that belongs to the flavivirus genus. The screen recovered twenty-one potential host proteins that modulate ZIKV replication in an IFN-dependent manner, including the previously known IFITM3 and LY6E. Further characterization contributed to delineate the spectrum of action of these genes towards other pathogenic RNA viruses, including Hepatitis C virus and SARS-CoV-2. Our data revealed that APOL3 acts as a proviral factor for ZIKV and several other related and unrelated RNA viruses. In addition, we showed that MTA2, a chromatin remodeling factor, possesses potent flavivirus-specific antiviral functions induced by IFN. Our work identified previously unrecognized genes that modulate the replication of RNA viruses in an IFN-dependent manner, opening new perspectives to target weakness points in the life cycle of these viruses.

Role and Limits of COVID-19 Vaccines in the Delicate Transition from Pandemic Mitigation to Endemic Control.

The recent surge of COVID-19 related to the Omicron variant emergence has thrown a harsh light upon epidemic control in the near future. This should lead the scientific and medical community to question the long-term vaccine strategy for SARS-CoV-2 control. We provide here a critical point of view regarding the virological evolution, epidemiological aspects, and immunological drivers for COVID-19 control, including a vaccination strategy. Overall, we need more innovations in vaccine development to reduce the COVID-19 burden long term. The most adequate answer might be better cooperation between universities, biotech and pharmaceutical companies.

A Myosin Vb Splice Variant Regulates Coronavirus M Protein Trafficking in Polarized Epithelial Cells

The membrane (M) glycoprotein of coronaviruses (CoVs) serves as the nidus for virion assembly. Using a yeast two‐hybrid screen, we identified the interaction of the cytosolic tail of Murine Hepatitis Virus (MHV‐CoV) M protein with Myosin Vb (MYO5B) (Figure 1A). MHV‐CoV M interacts specifically with the alternative splice variant of cellular MYO5B including Exon D (MYO5B+D), that also mediates interaction with cellular Rab10. When co‐expressed in human lung epithelial A549 and canine kidney epithelial MDCK cells, MYO5B+D co‐localized with MHV‐CoV M protein, as well as with M proteins from porcine epidemic diarrhea Virus (PEDV‐CoV), Middle East Respiratory Syndrome (MERS‐CoV) and Severe Acute Respiratory Syndrome 2 (SARS‐CoV‐2) (Figure 2). M‐GFP chimeric proteins co‐expressed with mCherry‐MYO5B+D also co‐localized with endogenous Rab10 and Rab11a (Figure 1B,C). We identified point mutations in MHV‐CoV M that blocked the interaction with MYO5B+D in yeast 2‐hybrid assays (Figure 1B). One of these point mutations (E121K) was previously shown to block MHV‐CoV virion assembly, and it blocked interaction with MYO5B+D. The E to K mutation at homologous positions in PEDV‐CoV, MERS‐CoV and SARS‐CoV‐2 M proteins also blocked colocalization with MYO5B+D. Knockdown of Rab10 blocked the co‐localization of the M proteins with MYO5B+D (Figure 2). Re‐expression of Cerulein‐Rab10 in Rab10 KD cells re‐established colocalization between M proteins and MYO5B+D (Figure 2). Our results suggest that the interaction of CoV M proteins with MYO5B+D may play a role in regulating their trafficking through Rab10‐containing membrane systems in epithelial cells.

sgDI-tector: defective interfering viral genome bioinformatics for detection of coronavirus subgenomic RNAs.

Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study the growing number of next-generation sequencing (NGS) data of SARS-CoV-2. We introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data. sgDI-tector allowed detection of sgRNA without initial knowledge of the transcription-regulatory sequences. We produced NGS data and successfully detected the nested set of sgRNAs with the ranking M > ORF3a > N>ORF6 > ORF7a > ORF8 > S > E>ORF7b. We also compared the level of sgRNA production with other types of viral RNA products such as defective interfering viral genomes.

A live measles-vectored COVID-19 vaccine induces strong immunity and protection from SARS-CoV-2 challenge in mice and hamsters.

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2.