Why HPV16? Why, now, HPV42? How the discovery of HPV42 in rare cancers provides an opportunity to challenge our understanding about the transition between health and disease for common members of the healthy microbiota DOI Creative Commons
Ignacio G. Bravo,

Sophia Belkhir,

Philippe Paget‐Bailly

et al.

FEMS Microbiology Reviews, Journal Year: 2024, Volume and Issue: 48(6)

Published: Nov. 1, 2024

Abstract In 2022, a bioinformatic, agnostic approach identified HPV42 as causative agent of rare cancer, later confirmed experimentally. This unexpected association offers an opportunity to reconsider our understanding about papillomavirus infections and cancers. We have expanded knowledge the diversity papillomaviruses diseases they cause. Yet, we still lack answers fundamental questions, such what makes HPV16 different from closely related HPV31 or HPV33; why very divergent HPV13 HPV32 cause focal epithelial hyperplasia, while HPV6 do not, despite their evolutionary relatedness. Certain members healthy skin microbiota are associated clinical conditions. propose that focus on cellular phenotypes, most often transient influenced by intrinsic extrinsic factors, may help understand continuum between health disease. A conceptual switch is required towards interpretation biology states connected transition probabilities, rather than quasi-deterministic programs. Under this perspective, only trigger malignant transformation when specific viral genotypes interact with precise states. Drawing Canguilhem’s concepts normal pathological, suggest fluid can illuminate how commensal-like benign malignant.

Language: Английский

Mysteries of adenovirus packaging DOI Creative Commons
Matthew Charman, Matthew D. Weitzman

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

ABSTRACT It is conventionally held that most DNA viruses package their genomes by one of two fundamental mechanisms: described the sequential or concurrent models assembly and packaging. Sequential packaging involves translocation a viral genome into pre-formed capsid, often referred to as pro-capsid. In contrast, does not require Instead, condensed, capsid shell formed around genome. The accumulation empty particles in adenovirus infected cells has led assumption may be best model. However, existing fail adequately explain all experimental observations, leaving many mysteries unresolved. this review, we describe key findings packaging, discuss them context competing versus We recent have redefined our understanding including role biomolecular condensates visualization situ . These advances renewed interest model anticipate lessons learned from will highly valuable for advancement vectors gene-delivery technologies. reviewing topic, hope stimulate discussion facilitate future investigation ultimately resolve gaps knowledge expand virus

Language: Английский

Citations

0
Activated blood-derived human primary T cells support replication of HAdV C5 and virus transmission to polarized human primary epithelial cells DOI Creative Commons
Daniela Sequeira, Maarit Suomalainen, Patrick C. Freitag

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

ABSTRACT Human adenoviruses (HAdVs) cause self-limiting disease but are life-threatening to immunocompromised individuals. HAdV-C5 infects epithelial cells of the airways and eyes through aerosols, contaminated hands, or medical instruments, as well fecal-oral contacts, gives rise viremia, persisting in lymphoid gastrointestinal tract. Here, we show that pre-activated human primary blood-derived T can be infected with vitro , upon incubation virus a mixture three distinct homotrimeric adapter proteins target cells. Each bind 1 12 fiber knobs virion designed ankyrin repeat protein. Two adapters contained single-chain antibody fragment cell surface CD3 CD28, third one cytokine interleukin-2. These mediated efficient infection by infectious progeny release, albeit donor-to-donor variability. Co-culture well-polarized air–liquid interface bronchial + gave progressively increased viral titers from replicating not replication-defective E1-deleted HAdV-C5, notably similar kinetics cell-free infections, suggesting was further amplified This study provides platform explore interactions between immune acute persistent settings. IMPORTANCE Many (HAdV), including infect propagate high airways. Virus ends up respiratory mucosa, where it persist subclinically for years, restricted memory humoral defense. In immunodeficient patients newborns, however, HAdV fatal, coincident lymphocytopenia proliferation activated lymphocytes productively coated trimerized targeting CD3, interleukin 2 receptors. A co-culture model absence HAdV-specific showed transferred led production compared alone, situation potentially mimicking persistently mucosal immunosuppressed patients.

Language: Английский

Citations

0
Clicking viruses—with chemistry toward mechanisms in infection DOI Creative Commons
Urs F. Greber

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

ABSTRACT Viruses subvert cells and evade host defense. They emerge unpredictably threaten humans livestock through their genetic phenotypic diversity. Despite more than 100 years since the discovery of viruses, molecular underpinnings virus infections are incompletely understood. The introduction new methodologies into field, such as that click chemistry some 10 ago, keeps uncovering facets viruses. Click uses bio-orthogonal reactions on chemical probes couples nucleic acids, proteins, lipids with tractable labels, fluorophores for single-cell single-molecule imaging, or biotin biochemical profiling infections. Its applications in single often achieve resolution provide important insights widely known phenomenon cell-to-cell infection variability. This review describes advances to unravel mechanisms a select set enveloped nonenveloped DNA RNA including adenovirus, herpesvirus, human immunodeficiency virus. It highlights recent breakthroughs viral DNA, RNA, protein, well host-derived lipid functions both live chemically fixed cells. discusses specific processes entry, uncoating, transcription, replication, packaging, assembly provides perspective explore cell biology, variability, genome organization particle.

Language: Английский

Citations

0
Induced tolerance to UV stress drives survival heterogeneity in isogenicE. colicell populations DOI Creative Commons
Shunsuke Ichikawa,

Midai Tanoue,

Junko S. Takeuchi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

The emergence of transiently tolerant bacterial subpopulations challenges our understanding stress tolerance mechanisms. While much is known about antibiotic tolerance, it remains unclear whether similar mechanisms contribute to survival under ultraviolet (UV) stress. Here, we employed a modified Luria-Delbrück fluctuation test investigate the presence pre-existing UV-tolerant in Escherichia coli . Our results showed no significant evidence pre-stress UV tolerance. Instead, data suggest that primarily driven by inducible DNA repair responses activated after exposure. Furthermore, sequential low-dose exposures yielded higher-than-expected survival, suggesting transient can be induced following initial exposure, likely through active processes. These findings indicate E. survives via an induced, rather than pre-existing, mechanism

Language: Английский

Citations

0
Why HPV16? Why, now, HPV42? How the discovery of HPV42 in rare cancers provides an opportunity to challenge our understanding about the transition between health and disease for common members of the healthy microbiota DOI Creative Commons
Ignacio G. Bravo,

Sophia Belkhir,

Philippe Paget‐Bailly

et al.

FEMS Microbiology Reviews, Journal Year: 2024, Volume and Issue: 48(6)

Published: Nov. 1, 2024

Abstract In 2022, a bioinformatic, agnostic approach identified HPV42 as causative agent of rare cancer, later confirmed experimentally. This unexpected association offers an opportunity to reconsider our understanding about papillomavirus infections and cancers. We have expanded knowledge the diversity papillomaviruses diseases they cause. Yet, we still lack answers fundamental questions, such what makes HPV16 different from closely related HPV31 or HPV33; why very divergent HPV13 HPV32 cause focal epithelial hyperplasia, while HPV6 do not, despite their evolutionary relatedness. Certain members healthy skin microbiota are associated clinical conditions. propose that focus on cellular phenotypes, most often transient influenced by intrinsic extrinsic factors, may help understand continuum between health disease. A conceptual switch is required towards interpretation biology states connected transition probabilities, rather than quasi-deterministic programs. Under this perspective, only trigger malignant transformation when specific viral genotypes interact with precise states. Drawing Canguilhem’s concepts normal pathological, suggest fluid can illuminate how commensal-like benign malignant.

Language: Английский

Citations

1