Biology subjects

Perbolianachis, P.

Publications and source records attributed to Perbolianachis, P..

5 recordsLinked to original sources

bioRxiv2026

Intra-host IRES heterogeneity shapes hepatitis C virus translation through epistatic and population-level effects

Hepatitis C virus (HCV) circulates within each patient as a diverse population of closely related genomes, yet RNA functional properties are commonly inferred from a single consensus or dominant genome. The contribution of non-coding intra-host variability, particularly within the internal ribosome entry site (IRES), to translational efficiency remains poorly defined. Here we investigated how naturally occurring HCV IRES variation influences viral RNA translation. Complete IRES sequences from chronically infected patients were analyzed using molecular cloning, bicistronic reporters, full-length replication-deficient viral RNAs and reconstructed intra-host populations. We found that natural IRES mutations displayed context-dependent effects, and combinations of mutations produced translational phenotypes that could not be predicted from the corresponding single mutations, consistent with intragenic epistasis. Moreover, several variants behaved differently in bicistronic reporters and full-length viral RNAs, demonstrating that both genomic and cellular context shape IRES function. Reconstructed genotype 1a populations largely reproduced the activity of their dominant haplotypes. In contrast, reconstructed genotype 3a populations translated substantially more efficiently than their corresponding dominant sequences, showing that low-frequency variants can collectively modulate translation at the population level. These findings demonstrate that the translational phenotype of HCV cannot always be inferred from the dominant sequence alone and identify epistasis, genomic context, and intra-host population composition as interacting determinants of viral RNA translation. ImportanceHepatitis C virus (HCV) exists within each infected person as a diverse population of closely related viruses rather than as a single genetic sequence. This study shows that natural variation in a key RNA region controlling viral protein production can alter how efficiently the virus functions, and that these effects depend on combinations of mutations rather than on individual changes alone. By analyzing complete viral RNAs in addition to widely used reporter systems, we demonstrate that the full viral genome can substantially influence the activity of this regulatory region, providing a more realistic view of how translation occurs during natural infection. Our findings also reveal that rare viral variants can collectively shape the behavior of the viral population, challenging the common practice of relying on a single dominant sequence to represent an infection. These results provide new insight into how genetic diversity drives HCV evolution and adaptation.

molecular biology↗

bioRxiv2026

IFNγ at the crossroads of systemic protection and brain vulnerability to coronavirus infection

The COVID-19 pandemic, together with previous outbreaks caused by highly pathogenic coronaviruses, highlighted the importance of understanding the host determinants that influence pathogenesis, both to improve our understanding of disease mechanisms, and to strengthen preparedness for future outbreaks. In our previous work we demonstrated dysregulation of IFN{gamma} response genes in COVID-19 patients, associated with both age and viral burden, positioning IFN{gamma} as a key mediator of host defense against SARS-CoV-2. Here, we used a preclinical murine model of coronavirus infection based on murine hepatitis virus (MHV-A59), widely validated for studying SARS-CoV-2 pathogenesis, together with IFN{gamma} knockout (IFN{gamma}-KO) mice to investigate the role of this cytokine during infection. We performed a comprehensive morphological, biochemical, hematological and proteomic characterization of infected wild-type (WT) and IFN{gamma}-deficient mice. Plasma proteomics revealed impaired inflammatory and coagulation-related responses in IFN{gamma}-KO animals compared to WT controls. We found increased viral load and infectious particles in peripheral organs, including liver, spleen, heart and muscle in IFN{gamma}-KO mice, whereas these were significantly reduced in the brain. Region-specific analysis further demonstrated decreased viral load in the prefrontal cortex and hippocampus of IFN{gamma}-KO animals. Consistently, bioinformatics analysis of transcriptomics data of IFN{gamma}-treated primary neuron cultures, together with frontal cortex from human COVID-19 patients, revealed activation of neuroinflammatory and neurological disease-associated pathways, supporting a role for IFN{gamma} in driving brain inflammatory responses during coronavirus infection. Together, these findings reveal a dual role for IFN{gamma} during coronavirus infection: it is important for controlling systemic viral dissemination and limiting peripheral tissue damage, yet it may also promote viral susceptibility and exacerbated inflammatory responses in the brain. These results support IFN{gamma} modulation as a potential therapeutic strategy to prevent or mitigate neurological complications associated with COVID-19. Author SummaryViral infections are controlled by the immune system, but the same responses that protect the body can sometimes contribute to tissue damage and disease. We investigated how a key immune molecule, called Interferon Gamma, influences the outcome of Coronavirus infection in different parts of the body. Using a mouse model of Coronavirus infection with Interferon Gamma deficiency, we found that this molecule plays two opposing roles: it helps control the spread of the virus throughout the body, but it also increases vulnerability of the brain to infection and inflammation. When this immune signal was absent, animals showed higher amounts of virus in several peripheral organs but surprisingly had lower levels of virus in specific brain regions. We further found that this immune response was associated with changes in inflammation and neurological processes in human data. Our findings reveal that antiviral immunity is not always uniformly protective and that its effects depend on the tissue involved. Understanding this balance may help guide future approaches to reduce virus-associated complications while preserving the protective functions of the immune response.

microbiology↗

bioRxiv2026

Extended tissue tropism and vertical transmission in a murine model of Mayaro virus infection

Mayaro virus (MAYV) is an emerging mosquito-borne alphavirus associated with acute febrile illness and persistent arthralgia, with increasing reports in Latin America and potential for geographic expansion. However, its dissemination dynamics, tissue tropism and transmission routes remain incompletely defined. Here, we developed a murine model to characterize systemic viral dissemination, tissue tropism and the impact of gestational stage on maternal-fetal outcomes. A nanoluciferase-expressing MAYV reporter enabled non-invasive in vivo imaging, revealing rapid and widespread systemic dissemination under controlled conditions. Complementary infection with wild-type (WT) virus confirmed broad tropism across lymphoid, musculoskeletal and reproductive tissues. At 24 hours post-infection (hpi), viral distribution was relatively homogeneous across tissues, whereas at 48 hpi, tissue-specific differences emerged, with increased viral loads in selected organs, including the spleen and male reproductive tissues. Transient sex-dependent differences were observed at 24 hpi but were not sustained at later time points. Hematological and biochemical analyses revealed early systemic alterations consistent with changes in leukocyte distribution during acute infection. Infectious viral particles were detected in reproductive tissues of both sexes, including in sperm, supporting the biological plausibility of non-vector transmission, although detection in exposed animals was limited. Gestational stage influenced infection outcomes: early gestation (infected at 7.5-8.5 dpc; analyzed at 9.5-10.5 dpc) was associated with detection of infectious virus in fetal tissues, whereas mid-gestation (infected at 13.5-14.5 dpc; analyzed at 15.5-16.5 dpc) showed no detectable infectious virus in fetuses despite evidence of viral antigen persistence and sustained infectious viral presence in maternal and placental compartments. Together, these findings provide a preclinical framework for investigating MAYV pathogenesis and underscore the role of tissue tropism and gestational context in shaping infection dynamics and maternal-fetal involvement. Author summaryMayaro virus (MAYV) is an emerging mosquito-borne virus that causes fever and long-lasting joint pain, with increasing reports in Latin America and potential for wider geographic spread. Despite its growing relevance, key aspects of MAYV pathogenesis remain to be fully defined, including the mechanisms underlying systemic dissemination and tissue tropism, as well as its potential to affect pregnancy or be transmitted through non-vector routes. Here, we used a mouse model with a luminescent reporter virus to track MAYV dissemination in vivo, revealing rapid and widespread distribution across multiple tissues. In studies using wild-type virus, infectious virus was detected not only in muscle and immune-related organs but also in reproductive tissues of both females and males. Importantly, gestational stage influenced viral distribution. When infection occurred early in gestation, infectious viral particles were detected in fetal tissues. In contrast, at later stages of pregnancy, infectious virus was no longer detectable in fetuses, despite evidence of viral antigen persistence and sustained infectious viral presence in maternal and placental tissues. Together, these findings advance our understanding of MAYV infection, highlight gestational timing as a factor associated with fetal exposure and suggest the possibility of transmission through routes other than mosquitoes, providing a framework for future studies on this emerging virus.

microbiology↗

bioRxiv2023

No evidence for highly pathogenic avian influenza virus H5N1 (clade 2.3.4.4b) in the Antarctic region during the austral summer 2022/23

The current highly pathogenic avian influenza H5N1 panzootic has substantial impacts on wild birds and marine mammals. Although major outbreaks occurred in South America, incursion to Antarctica emerged late in the breeding season of 2023/2024 and was confined the wider region of the Antarctic Peninsula. To infer potential underlying processes, we compiled H5N1 surveillance from Antarctica and Sub-Antarctic Islands prior to the first confirmed cases.

microbiology↗

bioRxiv2020

Evaluation Of SYBR Green Real Time PCR For Detecting SARS-CoV-2 From Clinical Samples

The pandemic caused by SARS-CoV-2 has triggered an extraordinary collapse of healthcare systems and hundred thousand of deaths worldwide. Following the declaration of the outbreak as a Public Health Emergency of International Concern by the World Health Organization (WHO) on January 30th, 2020, it has become imperative to develop diagnostic tools to reliably detect the virus in infected patients. Several methods based on real time reverse transcription polymerase chain reaction (RT-qPCR) for the detection of SARS-CoV-2 genomic RNA have been developed. In addition, these methods have been recommended by the WHO for laboratory diagnosis. Since all these protocols are based on the use of fluorogenic probes and one-step reagents (cDNA synthesis followed by PCR amplification in the same tube), these techniques can be difficult to perform given the limited supply of reagents in low and middle income countries. In the interest of economy, time and availability of chemicals and consumables, the SYBR Green-based detection was implemented to establish a convenient assay. Therefore, we adapted one of WHO recommended Taqman-based one-step real time PCR protocols (from the University of Hong Kong) to SYBR Green. Our results suggest that SYBR-Green detection represents a reliable cost-effective alternative to increase the testing capacity.

molecular biology↗