mBio® An ASM Access® Publication

The RIG-I-like receptors, RIG-I and MDA5, are innate sensors of RNA virus infections that are critical for mounting a robust antiviral immune response. Heme-oxidized IRP2 ligase 1 (HOIL1), a component of the linear ubiquitin chain assembly complex (LUBAC), is essential for interferon induction in response to viruses sensed by MDA5, but not viruses sensed by RIG-I; however, the underlying mechanism remains unclear. LUBAC contains two atypical E3 ubiquitin ligases, HOIL1 and HOIP. While HOIP...

Lumpy skin disease (LSD) is a severe transboundary disease of cattle caused by lumpy skin disease virus (LSDV), which is highly transmissible and responsible for substantial economic losses worldwide. Although cellular immune responses are critical for controlling poxvirus infections, the viral strategies used by LSDV to evade cytotoxic T-cell immunity remain poorly understood. In this study, we demonstrate that LSDV infection markedly downregulates major histocompatibility complex class I...

Influenza A virus produces three RNA species-viral RNA (vRNA), complementary RNA (cRNA), and messenger RNA (mRNA)-whose synthesis and trafficking are spatially compartmentalized. However, the high sequence similarity between cRNA and mRNA hinders their distinction in situ, limiting understanding of the spatial organization of the viral replication-transcription dynamics. Here, triple-lock fluorescence in situ hybridization (TriLock-FISH) was developed to distinguish vRNA, cRNA, and mRNA in situ...

Mitochondrial DNA (mtDNA) can exist in homoplasmic or heteroplasmic states, but the dynamics and stability of heteroplasmy remain poorly understood in fungal plant pathogens. Because a key fungicide target (cytochrome b) is encoded in the mitochondrial genome, understanding these mtDNA dynamics is crucial for predicting resistance development and evolution in agricultural pathosystems. In Zymoseptoria tritici, mutations G143A and Y132C in the quinone outside inhibitor-binding site of the...

Understanding how interspecific interactions shape ecosystem functioning is a fundamental and longstanding question in ecology, especially along an evolutionary trajectory. Here, we used experimental evolution to evaluate how microbial interactions and adaptive mutations shaped community-level functions in synthetic denitrifying communities (SDCs) along a species richness gradient (one, two, and six species). Our results showed that competitive microbial interactions were observed and...

Microsporidia such as Encephalitozoon hellem are obligate intracellular human parasites that remain genetically intractable, limiting the functional characterization of their proteomes. Experimental structural studies are challenging, as many proteins in microsporidia comprise a large percentage of disordered regions. Computational structural studies based on homology-based modeling and the use of deep-learning algorithms for microsporidian proteins also remain limited because most have little...

Pathogenic Leptospira transitions between environmental reservoirs and mammalian hosts, exposing the bacterium to distinct temperature conditions. Although Leptospira is generally considered to rely primarily on long-chain fatty acids for growth and to have limited capacity to use glucose, whether host-like temperature alters glucose-associated metabolic capacity remains unclear. Here, we used transcriptome-integrated genome-scale metabolic modeling to examine temperature-dependent metabolic...

Suppressive antiretroviral therapy (ART) in people with HIV (PWH) arrests progression to AIDS and onward viral transmission. However, viral transcription from integrated HIV-1 proviruses persists on treatment and is linked to markers of chronic immune activation, contributing to the accelerated development of comorbidities in PWH. Of particular interest are persistent responses in long-lived tissue-resident myeloid cells, which direct tissue-level inflammatory processes through cytokine...

Mycoviruses are widespread throughout the fungal kingdom and are known to infect diverse fungal taxa, including fungal species that are important plant and human pathogens. Although many mycoviruses have been found to have minimal effects on their host, several viruses have been found to modulate fungal physiology, and, as a result, impact fungal virulence. Screens for mycoviruses in clinically relevant fungi have identified numerous mycoviruses within several important human pathogens, but...

Members of Marine Group IV, now termed Hikarchaeia, hold an important transitional evolutionary position among Archaea but remain uncultivated, and their ecology remains uncharacterized. Over a 5-year period, we performed monthly profile sampling in the North Atlantic Subtropical Gyre and sequenced V4 16S rRNA gene amplicons, while also collecting additional size-fractionated and metagenomic samples. Hikarchaeal relative abundance annually peaked at ~1% of prokaryotic amplicons. Their relative...

Antibiotic efficacy is conventionally attributed to the susceptibility of the infecting pathogen. However, obese patients experience disproportionately poor infection outcomes despite receiving antibiotics to which pathogens remain genetically susceptible. These observations suggest that host-associated factors can influence treatment outcomes independently of the bacterial genotype, although the underlying mechanisms remain poorly understood. Using a mechanistic comparison of diet-induced obese...

Our knowledge of the nitrogen cycle has been advanced by the discovery of anammox bacteria, ammonia-oxidizing archaea, and comammox bacteria, along with their high diversity. Direct ammonia oxidation (dirammox), a recently discovered heterotrophic nitrification pathway, converts ammonium and organic nitrogen directly to N(2) through the DnfABC multienzyme system, further expanding our understanding of the nitrogen cycle. However, the taxonomic distribution, prevalence, and nitrogen metabolic...

Variable phytoplankton resource demands can buffer productivity to climate-driven declines in nutrient supply, but the extent of this buffering depends on limits to cellular elemental plasticity. Elemental plasticity is driven by a combination of genomic adaptation and physiological regulation, but their mechanistic links remain unresolved. Here, we combine continuous culture experiments with proteomics and elemental analyses to determine how genomic diversity shapes nutrient stress plasticity...

Human adenoviruses (HAdVs) are double-stranded DNA viruses that cause a wide range of diseases, including respiratory, ocular, and gastrointestinal infections. HAdVs rely extensively on alternative splicing to expand their coding capacity and regulate gene expression during infection. Using replication-competent epitope-tagged HAdV-C5 viruses, we investigated the function of a newly identified alternatively spliced viral transcript, 19K/IX, derived from the E1B19K and pIX genes. We show that the...

Infections due to Cryptococcus species are estimated to cause over 100,000 deaths a year. No cryptococcal vaccines are approved for human use. We have shown that vaccine formulations consisting of C. neoformans chitin deacetylase 2 (Cda2) and Cda1 adjuvanted with Cationic Adjuvant Formulation 01 (CAF01) protect mice against experimental cryptococcosis by a mechanism dependent upon CD4^(+) T cells. Here, using overlapping peptide libraries, we mapped epitopes in Cda2 and Cda1 that stimulated...