Search bioRxiv⌕ Search

Biology subjects

Korhonen, E. M.

Publications and source records attributed to Korhonen, E. M..

2 recordsLinked to original sources

Rat hepatitis E virus and novel paramyxoviruses in synanthropic rodents and shrews in Kenya

The majority of emerging infectious diseases are zoonotic, having their origin in wildlife before spilling over into the human population. While small mammals are recognized as critical reservoirs for these viruses, their viral diversity remains largely uncharacterized across many African countries. We conducted molecular surveillance of synanthropic rodents and shrews in the Kibera informal settlement in Nairobi and the rural Taita Hills region of Kenya to detect and characterize potential zoonotic viruses. Tissue samples from 228 rodents and shrews were screened for six viral families using PCR assays. Rat hepatitis E virus (HEV) (Rocahepevirus ratti), a rodent-associated virus with potential for human spillover, was identified in Mus musculus and Rattus norvegicus from Kibera. NGS was conducted for the HEV positive samples, and we obtained two near-complete HEV genomes from Rattus norvegicus, which clustered within rodent-associated HEV genotypes in the phylogenetic analysis. The two sequences from the Rattus norvegicus cluster together, indicating a close genetic relationship. Paramyxoviruses belonging to the genera Jeilongvirus and Parahenipavirus were detected both from Taita and Kibera in nine different samples from Rattus norvegicus, Mus minutoides, Crocidura sp and Acomys ignitus. One paramyxovirus positive sample (Acomys ignitus) from Taita was selected for further sequencing with NGS, and a complete genome of a new jeilongvirus was assembled. Phylogenetic analysis of the detected viruses confirmed the close relation to previously known rodent-borne jeilongviruses but also revealed potentially novel jeilong- and parahenipavirus species. Our findings highlight the circulation of potentially zoonotic viruses in both urban and rural small mammals in Kenya. It emphasizes the necessity of continued genomic surveillance of zoonotic viruses to mitigate risks of their spillover into human populations. HighlightsO_LISurveillance reveals diverse rodent-borne viruses circulating in Kenya. C_LIO_LIRat-HEV was detected in Rattus norvegicus and Mus musculus from an urban low-income area. C_LIO_LIParamyxoviruses were detected across multiple rodent and shrew species, including novel Acomys ignitus jeilongvirus. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/719784v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@86c94aorg.highwire.dtl.DTLVardef@10946adorg.highwire.dtl.DTLVardef@1ff45eforg.highwire.dtl.DTLVardef@4876f1_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

American mink as an animal model to study SARS-CoV-2 and vaccine response

Selecting a suitable animal model is crucial in understanding infectious diseases and developing vaccines. Here, we developed a receptor-binding domain -based SARS-CoV-2 vaccine with mouse Fc an immunopotentiator in a mink model. Four different variations of the vaccine were tested in groups of 30-31 American mink and followed for IgG and neutralizing antibodies (nAb) up to 27 weeks. Subcutaneous version induced a strong IgG and nAb response within two weeks and was still detectable at 27 weeks. Intranasal version also caused a detectable, although weaker, immune response. A simultaneously given subcutaneous vaccine against virus enteritis, botulism and hemorrhagic pneumonia potentially caused a lower SARS-CoV-2 antibody response, highlighting the need for further studies on co-effects of vaccines. In virus challenge with Alpha variant (B.1.1.7), vaccinated mink had a stronger antibody response than unvaccinated mink. Despite not preventing the infection, vaccinated mink had milder clinical signs and less virus in saliva. Another challenge of unvaccinated mink with Omicron variant showed similar results to alpha (BA.1) variant. Virus RNA was detected in the brain of unvaccinated mink but not vaccinated mink by in situ hybridization, indicating a suitability of mink to study neurological effects of SARS-CoV-2 and potentially long COVID as well. Author summaryFinding a good animal model is very important in studying infectious diseases and their treatment. The recent SARS-CoV2 pandemic highlighted this dilemma. We have developed an animal model based on mink due to their close match to humans in the symptomology of this disease. Such model will enable the study of relative susceptibility, transmission, tissue tropism, complex pathogenesis and long COVID, as well as prophylaxis and vaccines. This model will also help reduce the use of primates in this research. We have further developed a new vaccine for SARS-CoV2 based on the receptor binding domain of the S-protein with an inbuilt immune-enhancer. This vaccine underwent extensive testing in mink to determine response, long term protection, and safety. The vaccine was found to provide excellent titers of neutralizing antibodies with wide range in target variants. It also reduced the severity and duration of visible symptoms in the animals significantly. We propose this vaccine candidate for further study and future commercialization.

microbiology↗