Biology subjects

de Souza, W. M.

Publications and source records attributed to de Souza, W. M..

4 recordsLinked to original sources

bioRxiv2026

Acute IFN-gamma responses drive sensory neuron injury and chronic pain after chikungunya virus infection

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute and chronic musculoskeletal disease characterized by often debilitating pain; however, the mechanisms associated with the pain remain understudied. Here, we used an experimental mouse model and patients to investigate the role of interferon-{gamma} (IFN-{gamma}) in the pain during chronic inflammation after CHIKV infection. Our data show that CHIKV induces sustained joint inflammation, cartilage catabolism, and sensory neuron injury signatures, including Atf3 upregulation, but lacks detectable viral dissemination to dorsal root ganglia. We found that IFN-{gamma} expression was higher in CHIKV-infected joints, and direct IFN-{gamma} administration recapitulates mechanical hypersensitivity and neuronal stress independently of joint degeneration. Genetic or pharmacological disruption of IFN-{gamma} signalling prevented CHIKV-induced pain and neuronal stress without altering viral burden, demonstrating that IFN-{gamma} is required for both sensory dysfunction and joint pathology. By stratifying CHIKV-infected mice based on long-term nociceptive profiles, we show that persistent-pain subgroup characterized by elevated acute-phase systemic IFN-{gamma} and chronic peripheral neuropathic features. These findings were confirmed in human patients, where acute-phase IFN-{gamma} levels distinguished those who developed chronic arthralgia from those who recovered. Overall, our findings demonstrate that persistent post-CHIKV pain is driven by an IFN-{gamma}-mediated neuroimmune mechanism.

microbiology↗

bioRxiv2025

Molecular basis for shifted receptor recognition by an encephalitic arbovirus

After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors. Here, by determining cryo-electron microscopy structures of WEEV strains isolated from 1941-2005 bound to mammalian receptors, we identify polymorphisms in the WEEV spike protein that explain shifts in receptor dependencies and that can allow nonpathogenic strains to infect primary cortical neurons. We predict the receptor dependencies of additional strains and of a related North American alphavirus. Our findings have implications for outbreak preparedness and enhance understanding of arbovirus neurovirulence through virus receptor binding patterns.

microbiology↗

bioRxiv2023

Madariaga and Venezuelan equine encephalitis virus seroprevalence in rodent enzootic hosts in Eastern and Western Panama

While rodents are primary reservoirs of Venezuelan equine encephalitis virus (VEEV), their role in Madariaga virus (MADV) transmission remains uncertain, particularly given their overlapping geographic distribution. This study explores the interplay of alphavirus prevalence, rodent diversity, and land use within Darien and Western Panama provinces. A total of three locations were selected for rodent sampling in Darien province: Los Pavitos, El Real de Santa Maria and Santa Librada. Two sites were selected in Western Panama province: El Cacao and Ciri Grande. We used plaque reduction neutralization tests to assess MADV and VEEV seroprevalences in 599 rodents of 16 species across five study sites. MADV seroprevalence was observed at higher rates in Los Pavitos (Darien province), 9.0%, 95% CI: 3.6-17.6, while VEEV seroprevalence was elevated in El Cacao (Western Panama province), 27.3%, 95% CI: 16.1-40.9, and El Real de Santa Maria (Darien province), 20.4%, 95% CI: 12.6-29.7. Species like Oryzomys coesi, 23.1%, 95% CI: 5.0-53.8, and Transandinomys bolivaris, 20.0%, 95% CI: 0.5-71.6 displayed higher MADV seroprevalences than other species, whereas Transandinomys bolivaris, 80.0%, 95% CI: 28.3-99.4, and Proechimys semispinosus, 27.3%, 95% CI: 17.0-39.6, exhibited higher VEEV seroprevalences. Our findings provide support to the notion that rodents are vertebrate reservoirs of MADV and reveal spatial variations in alphavirus seropositivity among rodent species, with different provinces exhibiting distinct rates for MADV and VEEV. Moreover, specific rodent species are linked to unique seroprevalence patterns for these viruses, suggesting that rodent diversity and environmental conditions might play a significant role in shaping alphavirus distribution.

microbiology↗

bioRxiv2019

An ancient lineage of highly divergent parvoviruses infects both vertebrate and invertebrate hosts.

Chapparvoviruses are a highly divergent group of parvoviruses (family Parvoviridae) first identified in 2013. Interest in these poorly characterized viruses has been raised by recent studies indicating that they are the cause of chronic kidney disease that arises spontaneously in laboratory mice. In this study, we investigate the biological and evolutionary characteristics of chapparvoviruses via comparative analysis of genome sequence data. Our analysis, which incorporates sequences derived from endogenous viral elements (EVEs) as well as exogenous viruses, reveals that chapparvoviruses are an ancient lineage within the family Parvoviridae, clustering separately from members of both currently established parvoviral subfamilies. Consistent with this, they exhibit a number of characteristic genomic and structural features, i.e. a large number of putative auxiliary protein-encoding genes, capsid protein genes non-homologous to any hitherto parvoviral cap, as well as a putative capsid structure lacking the canonical fifth strand of the ABIDG sheet comprising the luminal side of the jelly roll. Our findings demonstrate that the chapparvovirus lineage infects an exceptionally broad range of host species, including both vertebrates and invertebrates. Furthermore, we observe that chapparvoviruses found in fish are more closely related to those from invertebrates than they are to those that infect amniote vertebrates. This suggests that transmission between distantly related host species may have occurred in the past. Our study provides the first integrated overview of the chapparvovirus group, and revises current views of parvovirus evolution\n\nAUTHOR SUMMARYChapparvoviruses are a recently identified group of viruses about which relatively little is known. However, recent studies have shown that these viruses cause disease in laboratory mice and are prevalent in the fecal virome of pigs and poultry, raising interest in their potential impact as pathogens, and utility as experimental tools. We examined the genomes of chapparvoviruses and endogenous viral elements ( fossilized virus sequences derived from ancestral viruses) using a variety of bioinformatics-based approaches. We show that the chapparvoviruses have an ancient origin and are evolutionarily distinct from all other related viruses. Accordingly, their genomes and virions exhibit a range of distinct characteristic features. We examine the distribution of these features in the light of chapparvovirus evolutionary history (which we can also infer from genomic data), revealing new insights into chapparvovirus biology.

evolutionary biology↗