Biology subjects

Kindrachuk, J.

Publications and source records attributed to Kindrachuk, J..

5 recordsLinked to original sources

bioRxiv2025

Zoonotic and Avian Pathogen Detections in Fecal and Sediment Samples - A Low-risk, High-throughput One Health Approach to Surveillance

Many pathogens, both those with human spillover potential as well as avian-specific viruses, are maintained in wild bird populations. While routine surveillance for influenza A viruses (IAVs) is performed annually, surveillance for other pathogens is limited. Sampling of wild birds is time-consuming, labour-intensive, often limited in sample size, and involves handling of wild and potentially infected birds, posing an increased risk of direct exposure for personnel. Additional methods for surveillance are needed given these significant challenges. Longitudinal fecal and sediment sampling was performed at various sites in southern Manitoba, Canada, particularly focused in Winnipeg from May to October 2025. Sites were chosen based on the suitability of the area for waterfowl habitat, the presence of waterfowl in the area, as well as proximity to reported outbreaks of H5N1 influenza virus. Fecal and sediment samples were collected and screened for the presence of influenza A virus (IAV), Newcastle disease virus (NDV), avian reovirus (ARV), and avian poxvirus (APXV). In total, 782 combined fecal and sediment samples were collected. Of the 714 fecal samples, 34 tested positive for IAV RNA (4.8% prevalence). None of the IAV-positive fecal samples tested positive for H5 RNA. Of the 68 sediments, 15 were positive for IAV RNA (22.1% prevalence), four of which were positive for H5 RNA. NDV RNA positivity was low, with only four positive fecal samples (0.6% prevalence) that were all collected on the same day. ARV RNA positivity was also low, with five positive sediment samples (7.4% prevalence in sediment samples). None of the samples tested positive for APXV DNA. This study builds on previous work showing the utility of environmental sampling for a variety of avian and zoonotic pathogens using a One Health approach that is low-risk, efficient, and high-throughput.

microbiology↗

bioRxiv2025

MPXV Clade IIb virus infection in mice leads to prolonged viral replication, macrophage infiltration, and decreased spermatogenesis in the testes.

Mpox (formerly monkeypox) is caused by monkeypox virus (MPXV) and has prompted two recent global health emergencies. Clade IIb MPXV, a recently recognized subclade, has been associated with oral and genital lesions and transmission among men who have sex with men (MSM); however, mechanisms of genital pathogenesis and sexual transmission are not understood. We investigated several routes of MPXV Clade IIb virus infection (intranasal, oral, anal, and intraperitoneal) and found high and prolonged viral titres in the testes after IP inoculation still detectable at 21 days. The testes had significant changes to tissue architecture including loss of spermatogenesis, disorganization of spermatozoa, loss of Leydig cells, and breakdown of the seminiferous tubule membranes. Viral antigen positive cells were present in the interstitial spaces between the seminiferous tubules with macrophage infiltration also evident. This work provides insights into potential of sexual transmission for MPXV viruses as well as mechanisms of Mpox disease which may significantly impact long-term fertility or sex organ health of infected males. Author SummaryMpox (formerly monkeypox) is a painful disease similar to smallpox caused by the monkeypox virus (MPXV) which is an emerging/re-emerging virus. Recently the WHO has declared two global health emergencies due to human-to-human transmission of MPXV. Clade IIb MPXV is a newly recognized subclade that has been associated with genital lesions and sexual transmission/contact; however, how the virus causes disease in sex-organs or how it is passed from person-to-person is not understood. We investigated several routes of MPXV Clade IIb inoculation and found IP inoculation in male mice led to high and prolonged viral titres in testes. Additionally, the testes were significantly affected having loss of sperm and cellular organization. Evidence of inflammatory cell infiltration, specifically, macrophages, are suspected to be the cause of testes specific disease. This work provides insights into potential of sexual transmission for MPXV viruses as well as mechanisms of Mpox disease.

microbiology↗

bioRxiv2023

The mitophagy receptor Nix coordinates nuclear calcium signaling to modulate the muscle phenotype.

Mitochondrial quality control is critical in muscle to ensure both contractile and metabolic function. Nix is a BCL-2 family member, mitophagy receptor, and has been implicated in muscle atrophy. Human GWAS suggests altered Nix expression could predispose to manifestations of mitochondrial disease. To interrogate Nix function, we generated a muscle-specific knockout model. Nix knockout mice displayed a ragged-red fibre phenotype, along with accumulation of mitochondria and endo/sarcoplasmic reticulum with altered morphology. Intriguingly, Nix knockout mice were more insulin sensitive with a corresponding increase in glycogen-rich muscle fibres. Kinome- and gene expression analyses revealed that Nix knockout impairs NFAT and canonical myostatin signaling, with alterations in muscle fibre-type composition and evidence of regeneration. Mechanistic experiments demonstrated that Nix modulates mitophagy, along with ER-phagy leading to altered nuclear calcium signaling. Collectively, these observations identify novel roles for Nix coordinating selective autophagy, oxidative gene expression, and signaling pathways that maintain the muscle phenotype.

cell biology↗

bioRxiv2021

SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

COVID-19 (coronavirus disease 2019) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

microbiology↗

bioRxiv2021

Male sex and age biases viral burden, viral shedding, and type 1 and 2 interferon responses during SARS-CoV-2 infection in ferrets

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and the elderly. Here we investigated the impact of male sex and age by infecting adult male, aged male, and adult female ferrets with SARS-CoV-2. Aged male ferrets had a decrease in temperature which was accompanied by prolonged viral replication with increased pathology in the upper respiratory tract after infection. Transcriptome analysis of the nasal turbinates and lungs indicated that female ferrets had significant increases in interferon response genes (OASL, MX1, ISG15, etc.) on day 2 post infection which was delayed in aged males. In addition, genes associated with taste and smell such as RTP1, CHGA, and CHGA1 at later time points were upregulated in males but not in females. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.

microbiology↗