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Studying Cryptosporidium Infection in 3D Tissue-derived Human Organoid Culture Systems by Microinjection
Published on: September 14, 2019
High infectivity and unique genomic sequence characteristics of Cryptosporidium parvum in China
Ruilian Jia1, Wanyi Huang2, Ni Huang2
1State Key Laboratory of Bioreactor Engineering, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai, China.
Abstract:
Zoonotic Cryptosporidium parvum infections are mainly caused by IIa and IId subtypes. As most biological characterizations have been performed on IIa subtypes, the biological and genetic characteristics of IId subtypes in China are not clear. We evaluated the infection and genetic characteristics of IId isolates in interferon-γ-knockout mice using qPCR to quantify oocyst shedding, histological examination to monitor pathological changes and comparative genomic analyses to identify infectivity and virulence-associated differences. Compared with the reference IIa isolate, mice infected with the IId isolates had significantly higher and longer oocyst shedding and lower body weight gain. In addition, the four IId isolates examined differed significantly in infectivity (as indicated by the median infective dose), oocyst shedding duration, and pathogenicity. Comparative genomic analysis indicated that the IId isolates had three more subtelomeric genes than the reference IIa isolate and 5385-5548 nucleotide substitutions, with the hypervariable genes mostly in two blocks on chromosome 1. In contrast, the four IId isolates differed from each other by 77-1,452 nucleotides, with virulence-associated sequence differences mainly in nine genes within a 28-kb block on chromosome 6. These data indicate the newly emerged C. parvum IId subtypes in China have high animal infectivity and unique genomic characteristics.
Insights
Newly identified Cryptosporidium parvum IId subtypes in China exhibit high animal infectivity and distinct genetic traits. These subtypes cause more severe infections in mice compared to the common IIa type.
Area of Science:
- Veterinary Parasitology
- Genomics
- Infectious Diseases
Background:
- Zoonotic Cryptosporidium parvum infections pose a significant public health concern.
- The IIa and IId subtypes are the primary causes of Cryptosporidium parvum infections.
- Limited biological and genetic data exist for the IId subtypes, particularly in China.
Purpose of the Study:
- To investigate the infection and genetic characteristics of Cryptosporidium parvum IId subtypes in China.
- To compare the infectivity, pathogenicity, and genomic features of IId subtypes with the reference IIa subtype.
- To identify genetic differences associated with infectivity and virulence in IId isolates.
Main Methods:
- Infection studies were conducted using interferon-γ-knockout mice.
- Quantitative polymerase chain reaction (qPCR) was used to measure oocyst shedding.
- Histological examination assessed pathological changes.
- Comparative genomic analyses were performed to identify genetic variations.
Main Results:
- Mice infected with IId isolates showed significantly higher and prolonged oocyst shedding and reduced body weight gain compared to IIa isolates.
- The four IId isolates exhibited significant variations in infectivity, oocyst shedding duration, and pathogenicity.
- Genomic analysis revealed IId isolates possess more subtelomeric genes and substantial nucleotide substitutions compared to IIa.
- Virulence-associated genetic differences in IId isolates were localized within specific chromosomal blocks.
Conclusions:
- The emerging Cryptosporidium parvum IId subtypes in China demonstrate high animal infectivity.
- These IId subtypes possess unique genomic characteristics that differentiate them from the IIa subtype.
- Understanding these characteristics is crucial for controlling Cryptosporidium parvum transmission and developing targeted interventions.
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