Results for “viral lifecycle disruption”

PubMed2026

Hydroxyl Radical Inactivation of Vesicle-Cloaked and Free Murine Norovirus: Linking Biomolecular Oxidation to Lifecycle Disruption and Infectivity Loss.

Hydroxyl radicals (•OH) play a central role in inactivating human viruses during advanced oxidation processes for water and wastewater treatment, solar disinfection, and natural attenuation in sunlit aquatic environments. Human norovirus, a leading cause of gastroenteritis, is efficiently transmitted through water and exhibits strong environmental persistence. The recent discovery of vesicle-cloaked virus clusters (viral vesicles) further challenges water treatment and reuse, particularly for norovirus elimination. We investigated •OH inactivation kinetics and mechanisms of murine norovirus 1 (MNV-1), a human norovirus surrogate, in free-virus and vesicle-cloaked forms. •OH rapidly inactivated both MNV-1 vesicles and free MNV-1 with second rate constants of ∼1010 M-1 s-1; however, the vesicle membrane provided a 2.24-fold protective effect to cloaked MNV-1, resulting in slower inactivation kinetics than those of free MNV-1. •OH oxidized viral capsid proteins and genomes together with vesicle proteins and lipids, resulting in impaired CD300lf receptor and cell-based binding, disrupted genome replication, and diminished viral assembly. Despite these biochemical and functional impairments, most vesicle structures remained largely intact following •OH exposure. This study establishes a quantitative framework linking biomolecular damage to viral infectivity loss through functional impairment and lifecycle disruption, providing mechanistic insights into advance water disinfection strategies and public health protection.

Norovirus↗

PubMed2026

Repurposing anti-phage defenses to differentially arrest the viral lifecycle reveals the regulatory logic of a parasitic satellite.

Mobile genetic elements frequently encode defense mechanisms to protect their bacterial hosts from viral attack. In Vibrio cholerae, these defensive elements include phage-inducible chromosomal island-like elements (PLEs), which are phage satellites that act as highly specialized parasites of the lytic phage ICP1. While PLE transcriptional activation upon ICP1 infection is known to be temporally regulated, the underlying regulatory logic and dependencies on the progression of the phage's developmental program required for activation remain unclear. In this study, we took a novel approach to define these dependencies by introducing independent anti-phage defense systems, BREX and DarTG, as molecular roadblocks to impede the ICP1 lifecycle. We discovered that, for both ICP1 and PLE, late-stage gene expression is fundamentally uncoupled from genome replication, representing a striking departure from the standard paradigm for double-stranded DNA phages. While BREX restricts ICP1 to an immediate-early transcriptional state that stalls PLE activation, DarTG allows the phage to execute its full transcriptional cascade despite the total block in DNA replication. This permissive environment provides the necessary cue(s) for complete PLE induction, revealing that robust PLE activation is profoundly dependent on the transcriptional progression of its helper phage.IMPORTANCEBacteria and their viruses (phages) are locked in perpetual evolutionary conflict. Some bacteria harbor phage satellites, specialized parasites that are activated to hijack the phage's components to spread all the while inhibiting viral production. While some satellites respond to a single viral trigger, the regulation of many satellites, including clinically relevant phage-inducible chromosomal island-like elements (PLEs) in Vibrio cholerae, remains poorly understood. Here, we used bacterial defense systems as molecular roadblocks to probe how PLE activation depends on its helper phage. We found that severe disruptions to viral transcription stall PLE activation. Unexpectedly, both the virus and the satellite can execute their full transcriptional programs even when DNA replication is completely blocked, challenging a fundamental paradigm in virology. These insights reveal a sophisticated level of phage-satellite coordination, illustrating how satellite activation is tightly linked to the transcriptional state of its helper phage, a dependency that ultimately drives the dissemination of mobile genetic elements.

Vibrio cholerae↗