bioRxiv Science⌕ Search

Biology subjects

Ralph-Altman, M.

Publications and source records attributed to Ralph-Altman, M..

2 recordsLinked to original sources

HSV-1 hijacks the DNA repair protein RAD51 at gene promoters to drive viral transcription

Productive infection by Herpes Simplex Virus type 1 (HSV-1) requires initiation of efficient viral gene expression. Upon nuclear entry, HSV-1 genomes are associated with several cellular factors, including DNA repair proteins. It is unclear how these cellular factors impact viral processes at early stages of infection. In this study, we investigate the role of RAD51, a core homologous recombination (HR) factor. We measured nascent viral transcription and show that RAD51 plays a pro-viral role in infection by promoting immediate-early viral gene expression. We demonstrate that RAD51 binds GC-rich gene promoter of ICP4 and directly promotes gene expression. We also reveal a previously unknown interaction between RAD51 and ADNP, a subunit of the ChAHP complex, known for its role in transcription regulation. We propose a model where RAD51 binds incoming genomes at promoter regions regulating the genome landscape and allowing for efficient transcription initiation.

cell biology↗

Potent Neutralization by Antibodies Targeting the Mpox A28 Protein

Mpox is the most pathogenic Poxvirus in circulation. While several antigens have been identified as targets for neutralizing antibodies, many proteins remain unexplored. We isolated and characterized four monoclonal antibodies (mAbs) targeting the Mpox A28 (OPG153), a virulence factor present on mature Mpox virions. The antibodies were isolated from convalescent individuals, alongside 14 additional mAbs targeting the A35 and H3 proteins. Anti-A28 mAbs potently neutralized Mpox and Vaccinia virus (VACV) through complement-dependent mechanisms involving C1q and C3 deposition. High resolution crystal structures of Anti-A28 mAbs 10M2146 and 8M2110 in complex with VACV A26 revealed two proximal epitopes within the N-terminal domain. Passive transfer of 8M2110 attenuated disease in infected mice. Moreover, immunization with A28 elicited antigen-specific B cells and robust neutralizing antibody responses and provided complete protection against lethal VACV challenge. These findings support Mpox A28 as a promising target for the induction of neutralizing antibodies and antiviral interventions.

immunology↗