The Magic Staff: A Comprehensive Overview of Baculovirus-Based Technologies Applied to Human and Animal Health

Baculoviruses are enveloped, insect-specific viruses with large double-stranded DNA genomes. Among all the baculovirus species, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the most studied. Due to its characteristics regarding biosafety, narrow host range and the availability of different platforms for modifying its genome, AcMNPV has become a powerful biotechnological tool. In this review, we will address the most widespread technological applications of baculoviruses. We will begin by summarizing their natural cycle both in larvae and in cell culture and how it can be exploited. Secondly, we will explore the different baculovirus-based protein expression systems (BEVS) and their multiple applications in the pharmaceutical and biotechnological industry. We will focus particularly on the production of vaccines, many of which are either currently commercialized or in advanced stages of development (e.g., Novavax, COVID-19 vaccine). In addition, recombinant baculoviruses can be used as efficient gene transduction and protein expression vectors in vertebrate cells (e.g., BacMam). Finally, we will extensively describe various gene therapy strategies based on baculoviruses applied to the treatment of different diseases. The main objective of this work is to provide an extensive up-to-date summary of the different biotechnological applications of baculoviruses, emphasizing the genetic modification strategies used in each field

Prokaryotic membrane coat - like proteins: An update

Membrane coat proteins are essential players in the eukaryotic endomembrane traffic system. Previous work identified proteins with the membrane-coat architecture in prokaryotes, specifically in the Planctomycetes, Verrucomicrobia and Chlamydiae (PVC) superphylum, bacteria that display the most developed prokaryotic endomembrane system. Hence, the membrane coat-like (MCL) proteins are predicted to play a central role in this system but their actual function is still unknown. In this work we strengthened previous structure predictions for these prokaryotic MCL proteins. We also detected new putative MCL proteins in the Planctomycete Gemmata obscuriglobus. Structural analysis of these revealed the presence of additional domains apart from the β-propeller and α-solenoid combination, characteristic of the membrane-coat architecture. Functions associated with these domains include some related to carbohydrate or membrane/lipid binding. Using homology-based methods, we found MCL proteins in other bacterial phyla, but the most abundant hits are still restricted to Planctomycetes and Verrucomicrobia. Detailed inspection of neighbouring genes of MCL in G. obscuriglobus supports the idea that the function of these proteins is related to membrane manipulation. No significant hits were found in Archaea, including Asgard archaea. More than 10 years after their original detection, PVC bacteria are still uniquely linked to eukaryotes through the structure of the MCL proteins sustaining their endomembrane system.This work was realised under the framework of the MSC program REFRACT MSCA RISE PROJECT 2019 (H2020 EU GA N 823886). This work was also supported by Mineco, SP (Grant No. PID2020-119733GB-I00) and the “Moore-Simons Project on the Origin of the Eukaryotic Cell” (Grant No. 9733/ DOI https://doi.org/10.37807/GBMF9733) to DPD.Peer reviewe