Biology subjects

Nigg, J.

Publications and source records attributed to Nigg, J..

6 recordsLinked to original sources

bioRxiv2026

Parasitism to mutualism shift during a viral infection in Drosophila under thermal stress

Host-parasite interactions exist along a continuum from parasitism to mutualism, yet the environmental drivers governing transitions along this spectrum remain underexplored. Here we show that chronic thermal stress systematically attenuates virulence across multiple natural RNA viruses in Drosophila melanogaster and shifts persistent Nora virus infection into conditional mutualism, enhancing host lifespan, reproductive output, and behavioral performance without compromising viral persistence. Driven by host immunometabolic reprogramming and aging deceleration rather than viral genomic adaptation, this phenotypic switch demonstrates that thermal stress can invert the sign of biotic interactions. Our findings establish that persistent infections can expand host thermal reaction norms in animals, revealing how climate warming can fundamentally alter selection pressures and host-pathogen coevolutionary trajectories.

microbiology↗

bioRxiv2025

The pupal stage is a developmental window for RNA virus persistence in Drosophila

RNA viruses establish persistent infections in insects through mechanisms that are not fully understood. We focused on three positive-sense RNA viruses that naturally establish persistent infections: Drosophila A virus (DAV), Drosophila C virus (DCV), and Nora virus. We examined how these viruses interact with their hosts during development and we found that pupal metamorphosis is a critical window where virus-host immune interactions influence persistence differently across viruses. Peak viral loads and replication occur during pupation, coinciding with increased endogenous reverse transcriptase activity. Notably, reverse transcription of viral RNA genomes produces viral DNA (vDNA) forms of DAV and DCV that are first detectable during pupation and are involved in persistence. In contrast, Nora virus achieves persistence without detectable vDNA. Immune responses during pupation are virus-specific, involving suppression of RNA interference components and varied regulation of JAK-STAT signaling. After metamorphosis, DAV continues producing vDNA into adulthood while DCV shows transient vDNA production, and Nora virus bypasses vDNA production altogether. These findings point to pupation as a key developmental stage for the establishment of persistent infections through distinct viral persistence strategies.

microbiology↗

bioRxiv2025

Microbiome composition modulates the lethal outcome of Drosophila A virus infection

Host-associated microbiomes can strongly influence viral infection outcomes, yet how minor variations in commensal bacterial composition modulate viral pathogenesis remain poorly understood. Here, we used Drosophila melanogaster to investigate how bacterial microbiome composition affects pathogenesis of enteric RNA viruses. Lactiplantibacillus plantarum supplementation increased bacterial microbiome diversity without altering total bacterial load, while Acetobacter pomorum supplementation had minimal impact on the bacterial microbiome. L. plantarum-enriched flies exhibited an additional [~]15% reduction in lifespan from Drosophila A virus (DAV) infection despite showing reduced viral protein accumulation and similar viral RNA levels. The reduction in tolerance to viral infection required live bacteria and was observed only for DAV, as no change in mortality was observed with Nora virus or Drosophila C virus infections. Mechanistic investigations revealed that tolerance reduction occurs independently of transcriptional immune responses, as DAV-infected flies showed similar transcriptional profiles regardless of bacterial microbiome composition. Intestinal barrier function assays demonstrated that L. plantarum-supplemented flies died before developing signs of gut barrier disruption, suggesting that extra-intestinal mechanisms contribute to mortality; this interpretation is further supported by similar levels of intestinal damage markers observed in virus-infected flies under both microbiome conditions. Viral genomic sequencing ruled out microbiome-driven selection of more pathogenic viral variants, as no adaptive mutations were observed between microbiome conditions that could account for the differential pathogenesis. These findings describe how subtle shifts in microbiome composition modulate viral infection outcomes through pathways that operate independently of canonical immune responses, viral evolution, and intestinal damage.

microbiology↗

bioRxiv2025

Macrodomain ADP-ribose binding but not ADP-ribosylhydrolase activity is critical for chikungunya virus infection of Aedes mosquitoes

Viral macrodomains are promising antiviral targets that counteract host ADP-ribosylation-mediated antiviral responses in mammals. However, their role in dual-host viruses within the mosquito vector remains largely unknown. Here, we investigated the role of the Chikungunya virus (CHIKV) nsP3 macrodomain catalytic activity by mutating the active-site asparagine 24 (N24). N24 mutant viruses rapidly selected for compensatory second-site mutations at aspartate 31 (D31) in mammalian Vero cells, while interferon-competent human cells favored reversion at position 24 instead, suggesting adaptive responses to macrodomain functional impairment. Catalytically inactive double-mutant viruses replicated poorly in interferon-competent human cells but comparably to wild-type in mosquito cells. In Aedes mosquitoes in vivo, macrodomain mutations modulated CHIKV replication and infectivity in a mutation-specific manner: one mutant reduced them while another enhanced them. Biochemical and structural analyses confirmed that these phenotypes arise in the context of a catalytically inactive macrodomain that retains ADP-ribose binding capacity, with D31 mutations lining the substrate exit path. These findings demonstrate that macrodomain catalytic activity modulates CHIKV dissemination and transmission potential in Aedes mosquitoes, revealing fundamental differences in host-dependent evolutionary advantage for a catalytically inactive viral enzyme.

molecular biology↗

bioRxiv2025

Persistent viral infections impact key biological traits in Drosophila melanogaster

Persistent viral infections have been assumed to impose minimal fitness costs for insects. We established persistent mono-infections of Drosophila melanogaster with four different enteric RNA viruses: Drosophila A virus (DAV), Drosophila C virus (DCV), Bloomfield virus, and Nora virus. We observed that these infections significantly reduce fly survival, alter the number of viable offspring per female, modulate microbiome composition, impact locomotor abilities, and change activity patterns. These results demonstrate the significant impact of persistent viral infections on key biological traits and expand our understanding of the fitness costs of persistent viral infections for the host. In addition, the four viruses displayed different accumulation kinetics and elicited unique transcriptional profiles with no common core responses. The transcriptional changes triggered by DCV infection persisted even after viral clearance. This comprehensive comparative dataset represents a valuable resource for researchers studying host-pathogen interactions, providing detailed transcriptional profiles, and behavioral measurements across different viral infections and time points. Our findings reveal that persistent viral infections modulate critical aspects of insect biology, affecting host physiology and behavior.

microbiology↗

bioRxiv2018

Individual differences in functional brain connectivity predict temporal discounting preference in the transition to adolescence

The transition from childhood to adolescence is marked by distinct changes in behavior, including how one values waiting for a large reward compared to receiving an immediate, yet smaller, reward. While previous research has emphasized the relationship between this preference and age, it is also proposed that this behavior is related to circuitry between valuation and cognitive control systems. In this study, we examined how age and intrinsic functional connectivity strength within and between these neural systems relate to changes in discounting behavior across the transition into adolescence. We used mixed-effects modeling and linear regression to assess the contributions of age and connectivity strength in predicting discounting behavior. First, we identified relevant connections in a longitudinal sample of 64 individuals who completed MRI scans and behavioral assessments 2-3 times across ages 7-15 years (137 scans). We then repeated the analysis in a separate, cross-sectional, sample of 84 individuals (7-13 years). Both samples showed an age-related increase in preference for waiting for larger rewards. Connectivity strength within and between valuation and cognitive control systems accounted for further variance not explained by age. These results suggest that individual differences in functional neural organization can account for behavioral changes typically associated with age.

neuroscience↗