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1. Author Correction: Time-series sewage metagenomics distinguishes seasonal, human-derived and environmental microbial communities potentially allowing source-attributed surveillance

Author

Becsei, Ágnes, Fuschi, Alessandro, Otani, Saria, Kant, Ravi, Weinstein, Ilja, Alba, Patricia, Stéger, József, Visontai, Dávid, Brinch, Christian, de Graaf, Miranda, Schapendonk, Claudia M. E., Battisti, Antonio, De Cesare, Alessandra, Oliveri, Chiara, Troja, Fulvia, Sironen, Tarja, Vapalahti, Olli, Pasquali, Frédérique, Bányai, Krisztián, Makó, Magdolna, Pollner, Péter, Merlotti, Alessandra, Koopmans, Marion, Csabai, Istvan, Remondini, Daniel, Aarestrup, Frank M., and Munk, Patrick

Published
2024
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2. Time-series sewage metagenomics distinguishes seasonal, human-derived and environmental microbial communities potentially allowing source-attributed surveillance

Author

Becsei, Ágnes, Fuschi, Alessandro, Otani, Saria, Kant, Ravi, Weinstein, Ilja, Alba, Patricia, Stéger, József, Visontai, Dávid, Brinch, Christian, de Graaf, Miranda, Schapendonk, Claudia M. E., Battisti, Antonio, De Cesare, Alessandra, Oliveri, Chiara, Troja, Fulvia, Sironen, Tarja, Vapalahti, Olli, Pasquali, Frédérique, Bányai, Krisztián, Makó, Magdolna, Pollner, Péter, Merlotti, Alessandra, Koopmans, Marion, Csabai, Istvan, Remondini, Daniel, Aarestrup, Frank M., and Munk, Patrick

Published
2024
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3. Signal peptide mimicry primes Sec61 for client-selective inhibition.

Author

Rehan, Shahid, Tranter, Dale, Sharp, Phillip, Craven, Gregory, Lowe, Eric, Anderl, Janet, Muchamuel, Tony, Abrishami, Vahid, Kuivanen, Suvi, Jennings, Andy, Kalyanaraman, Chakrapani, Strandin, Tomas, Javanainen, Matti, Vapalahti, Olli, McMinn, Dustin, Kirk, Christopher, Huiskonen, Juha, Paavilainen, Ville, Jacobson, Matthew, Taunton, Jack, and Wenzell, Nicole

Subjects
Animals, Mice, Protein Sorting Signals, Protein Transport, Membrane Proteins, SEC Translocation Channels, Protein Biosynthesis
Abstract

Preventing the biogenesis of disease-relevant proteins is an attractive therapeutic strategy, but attempts to target essential protein biogenesis factors have been hampered by excessive toxicity. Here we describe KZR-8445, a cyclic depsipeptide that targets the Sec61 translocon and selectively disrupts secretory and membrane protein biogenesis in a signal peptide-dependent manner. KZR-8445 potently inhibits the secretion of pro-inflammatory cytokines in primary immune cells and is highly efficacious in a mouse model of rheumatoid arthritis. A cryogenic electron microscopy structure reveals that KZR-8445 occupies the fully opened Se61 lateral gate and blocks access to the lumenal plug domain. KZR-8445 binding stabilizes the lateral gate helices in a manner that traps select signal peptides in the Sec61 channel and prevents their movement into the lipid bilayer. Our results establish a framework for the structure-guided discovery of novel therapeutics that selectively modulate Sec61-mediated protein biogenesis.

Published
2023

4. Phylogenetic Characterization of Orthohantavirus dobravaense (Dobrava Virus)

Author

Erdin, Mert, Polat, Ceylan, Smura, Teemu, Irmak, Sercan, Cetintas, Ortac, Cogal, Muhsin, Colak, Faruk, Karatas, Ahmet, Sozen, Mustafa, Matur, Ferhat, Vapalahti, Olli, Sironen, Tarja, and Oktem, Ibrahim Mehmet Ali

Subjects
Prevention, Analysis, Risk factors, Hemorrhagic fevers -- Risk factors -- Prevention, Virus diseases -- Risk factors -- Prevention, Phylogeny -- Analysis, Hemorrhagic fever -- Risk factors -- Prevention
Abstract

Orthohantaviruses are globally distributed. Until now, they have been detected in rodents, insectivores, and bats. Rodentborne orthohantaviruses, which are associated with human diseases, are divided into 3 major groups, murid-borne, [...]

Published
2024
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5. Ancestral allele of DNA polymerase gamma modifies antiviral tolerance

Author

Kang, Yilin, Hepojoki, Jussi, Maldonado, Rocio Sartori, Mito, Takayuki, Terzioglu, Mügen, Manninen, Tuula, Kant, Ravi, Singh, Sachin, Othman, Alaa, Verma, Rohit, Uusimaa, Johanna, Wartiovaara, Kirmo, Kareinen, Lauri, Zamboni, Nicola, Nyman, Tuula Anneli, Paetau, Anders, Kipar, Anja, Vapalahti, Olli, and Suomalainen, Anu

Published
2024
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6. Infective SARS-CoV-2 in Skull Sawdust at Autopsy, Finland

Author

Kantonen, Jonas N., Kuivanen, Suvi, Smura, Teemu, Puttonen, Henri, Kekalainen, Eliisa, Sajantila, Antti, Myllykangas, Liisa, Kantele, Anu, Vapalahti, Olli, Mayranpaa, Mikko I., and Carpen, Olli

Subjects
Research, Risk factors, Causes of, Health aspects, Aerosols -- Health aspects, Sawing -- Health aspects, Dust -- Health aspects, Disease transmission -- Risk factors, Medical research, Occupational exposure -- Research, Autopsy -- Research, COVID-19 -- Causes of -- Risk factors, Medicine, Experimental, Occupational health and safety -- Research
Abstract

Autopsies afford simultaneous access to all tissues and body compartments. The unique opportunity for extensive sampling during autopsy enables several research questions to be addressed. Early in the COVID-19 pandemic, [...]

Published
2024

10. Partial Genome Characterization of Novel Parapoxvirus in Horse, Finland

Author

Virtanen, Jenni, Hautaniemi, Maria, Dutra, Lara, Plyusnin, Ilya, Hautala, Katja, Smura, Teemu, Vapalahti, Olli, Sironen, Tarja, Kant, Ravi, and Kinnunen, Paula M.

Subjects
Identification and classification, Genetic aspects, Causes of, Horse diseases -- Causes of, Poxviruses -- Identification and classification -- Genetic aspects, DNA virus infections -- Causes of, Dermatitis -- Causes of, DNA viruses -- Identification and classification -- Genetic aspects, Skin -- Inflammation, Horses -- Diseases
Abstract

Parapoxviruses (PPVs) usually cause contagious skin infections in ruminants and occasionally infect other species such as humans (1). The genus Parapoxvirus encompasses the following recognized species: Orf virus, bovine papular [...]

Published
2023
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11. The phylodynamics of SARS-CoV-2 during 2020 in Finland.

Author

Truong Nguyen, Phuoc, Kant, Ravi, Van den Broeck, Frederik, Suvanto, Maija T, Alburkat, Hussein, Virtanen, Jenni, Ahvenainen, Ella, Castren, Robert, Hong, Samuel L, Baele, Guy, Ahava, Maarit J, Jarva, Hanna, Jokiranta, Suvi Tuulia, Kallio-Kokko, Hannimari, Kekäläinen, Eliisa, Kirjavainen, Vesa, Kortela, Elisa, Kurkela, Satu, Lappalainen, Maija, Liimatainen, Hanna, Suchard, Marc A, Hannula, Sari, Ellonen, Pekka, Sironen, Tarja, Lemey, Philippe, Vapalahti, Olli, and Smura, Teemu

Subjects
SARS-CoV-2, Viral epidemiology, Pneumonia & Influenza, Vaccine Related, Biodefense, Emerging Infectious Diseases, Prevention, Infectious Diseases, Infection, Good Health and Well Being
Abstract

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections and fatalities globally since its emergence in late 2019. The virus was first detected in Finland in January 2020, after which it rapidly spread among the populace in spring. However, compared to other European nations, Finland has had a low incidence of SARS-CoV-2. To gain insight into the origins and turnover of SARS-CoV-2 lineages circulating in Finland in 2020, we investigated the phylogeographic and -dynamic history of the virus.MethodsThe origins of SARS-CoV-2 introductions were inferred via Travel-aware Bayesian time-measured phylogeographic analyses. Sequences for the analyses included virus genomes belonging to the B.1 lineage and with the D614G mutation from countries of likely origin, which were determined utilizing Google mobility data. We collected all available sequences from spring and fall peaks to study lineage dynamics.ResultsWe observed rapid turnover among Finnish lineages during this period. Clade 20C became the most prevalent among sequenced cases and was replaced by other strains in fall 2020. Bayesian phylogeographic reconstructions suggested 42 independent introductions into Finland during spring 2020, mainly from Italy, Austria, and Spain.ConclusionsA single introduction from Spain might have seeded one-third of cases in Finland during spring in 2020. The investigations of the original introductions of SARS-CoV-2 to Finland during the early stages of the pandemic and of the subsequent lineage dynamics could be utilized to assess the role of transboundary movements and the effects of early intervention and public health measures.

Published
2022

18. Human-derived air–liquid interface cultures decipher Alzheimer’s disease–SARS-CoV-2 crosstalk in the olfactory mucosa

Author

Shahbaz, Muhammad Ali, Kuivanen, Suvi, Lampinen, Riikka, Mussalo, Laura, Hron, Tomáš, Závodná, Táňa, Ojha, Ravi, Krejčík, Zdeněk, Saveleva, Liudmila, Tahir, Numan Ahmad, Kalapudas, Juho, Koivisto, Anne M., Penttilä, Elina, Löppönen, Heikki, Singh, Prateek, Topinka, Jan, Vapalahti, Olli, Chew, Sweelin, Balistreri, Giuseppe, and Kanninen, Katja M.

Published
2023
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20. Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants

Author

Mäkelä, Anna R., Uğurlu, Hasan, Hannula, Liina, Kant, Ravi, Salminen, Petja, Fagerlund, Riku, Mäki, Sanna, Haveri, Anu, Strandin, Tomas, Kareinen, Lauri, Hepojoki, Jussi, Kuivanen, Suvi, Levanov, Lev, Pasternack, Arja, Naves, Rauno A., Ritvos, Olli, Österlund, Pamela, Sironen, Tarja, Vapalahti, Olli, Kipar, Anja, Huiskonen, Juha T., Rissanen, Ilona, and Saksela, Kalle

Published
2023
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21. Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein

Author

Yang, Kailu, Wang, Chuchu, Kreutzberger, Alex J. B., Ojha, Ravi, Kuivanen, Suvi, Couoh-Cardel, Sergio, Muratcioglu, Serena, Eisen, Timothy J., White, K. Ian, Held, Richard G., Subramanian, Subu, Marcus, Kendra, Pfuetzner, Richard A., Esquivies, Luis, Doyle, Catherine A., Kuriyan, John, Vapalahti, Olli, Balistreri, Giuseppe, Kirchhausen, Tom, and Brunger, Axel T.

Published
2022

22. SARS-CoV-2 requires acidic pH to infect cells

Author

Kreutzberger, Alex J. B., Sanyal, Anwesha, Saminathan, Anand, Bloyet, Louis-Marie, Stumpf, Spencer, Liu, Zhuoming, Ojha, Ravi, Patjas, Markku T., Geneid, Ahmed, Scanavachi, Gustavo, Doyle, Catherine A., Somerville, Elliott, Da Cunha Correia, Ricardo Bango, Di Caprio, Giuseppe, Toppila-Salmi, Sanna, Mäkitie, Antti, Kiessling, Volker, Vapalahti, Olli, Whelan, Sean P. J., Balistreri, Giuseppe, and Kirchhausen, Tom

Published
2022

24. No Substantial Histopathologic Changes in Mops condylurus Bats Naturally Infected with Bombali Virus, Kenya

Author

Kareinen, Lauri, Airas, Niina, Kotka, Sara T., Masika, Moses M., Aaltonen, Kirsi, Anzala, Omu, Ogola, Joseph, Webala, Paul W., Vapalahti, Olli, Sironen, Tarja, and Forbes, Kristian M.

Subjects
Control, Identification and classification, Observations, Diseases, Prevention, Risk factors, Bats (Animals) -- Observations -- Diseases, Marburg virus disease -- Risk factors -- Prevention, Ebola virus -- Identification and classification -- Control, Bats -- Observations -- Diseases
Abstract

Despite extensive research since the first documented human Ebola virus (EBOV) disease outbreak in 1976, animal species involved and mechanisms by which ebolaviruses spillover to humans remains enigmatic. Bats have [...]

Published
2023
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25. Intrahost Monkeypox Virus Genome Variation in Patient with Early Infection, Finland, 2022

Author

Vauhkonen, Hanna, Kallio-Kokko, Hannimari, Hiltunen-Back, Eija, Lonnqvist, Lasse, Leppaaho-Lakka, Jaana Mannonen, Laura, Kant, Ravi, Sironen, Tarja, Kurkela, Satu, Lappalainen, Maija, Zorec, Tomaz Mark, Zakotnik, Samo, Vlaj, Doroteja, Korva, Misa, Avsic-Zupanc, Tatjana, Poljak, Mario, Smura, Teemu, and Vapalahti, Olli

Subjects
Diagnosis, Genetic aspects, Case studies, Mpox -- Diagnosis -- Genetic aspects -- Case studies, Genetic variation -- Case studies, Human monkeypox -- Diagnosis -- Genetic aspects -- Case studies
Abstract

During 2022, an unprecedented multicountry outbreak of monkeypox virus (MPXV) infection among humans was detected. The first verified mpox cases in Europe were reported in mid-May 2022 with no apparent [...]

Published
2023
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26. Image-based and machine learning-guided multiplexed serology test for SARS-CoV-2

Author

Pietiäinen, Vilja, Polso, Minttu, Migh, Ede, Guckelsberger, Christian, Harmati, Maria, Diosdi, Akos, Turunen, Laura, Hassinen, Antti, Potdar, Swapnil, Koponen, Annika, Sebestyen, Edina Gyukity, Kovacs, Ferenc, Kriston, Andras, Hollandi, Reka, Burian, Katalin, Terhes, Gabriella, Visnyovszki, Adam, Fodor, Eszter, Lacza, Zsombor, Kantele, Anu, Kolehmainen, Pekka, Kakkola, Laura, Strandin, Tomas, Levanov, Lev, Kallioniemi, Olli, Kemeny, Lajos, Julkunen, Ilkka, Vapalahti, Olli, Buzas, Krisztina, Paavolainen, Lassi, Horvath, Peter, and Hepojoki, Jussi

Published
2023
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28. Introduction and Rapid Spread of SARS-CoV-2 Omicron Variant and Dynamics of BA.1 and BA.1.1 Sublineages, Finland, December 2021

Author

Vauhkonen, Hanna, Nguyen, Phuoc Truong, Kant, Ravi, Plyusnin, Ilja, Erdin, Mert, Kurkela, Satu, Liimatainen, Hanna, Ikonen, Niina, Blomqvist, Soile, Liitsola, Kirsi, Lindh, Erika, Helve, Otto, Jarva, Hanna, Loginov, Raisa, Palva, Aino, Hannunen, Tiina, Hannula, Sari, Parry, Mikko, Kauppi, Paula, Vaheri, Antti, Sironen, Tarja, Lappalainen, Maija, Savolainen-Kopra, Carita, Smura, Teemu, and Vapalahti, Olli

Subjects
Statistics, Identification and classification, Distribution, Causes of, Company distribution practices, SARS-CoV-2 variants -- Identification and classification -- Distribution, Epidemics -- Statistics -- Causes of -- Finland, COVID-19 -- Statistics -- Causes of
Abstract

The most recent SARS-CoV-2 variant of concern, Omicron (Pango lineage B.1.1.529), was first detected in South Africa (1), although it might have emerged elsewhere, and has since spread globally at [...]

Published
2022
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31. Semen inhibits Zika virus infection of cells and tissues from the anogenital region.

Author

Müller, Janis A, Harms, Mirja, Krüger, Franziska, Groß, Rüdiger, Joas, Simone, Hayn, Manuel, Dietz, Andrea N, Lippold, Sina, von Einem, Jens, Schubert, Axel, Michel, Manuela, Mayer, Benjamin, Cortese, Mirko, Jang, Karen S, Sandi-Monroy, Nathallie, Deniz, Miriam, Ebner, Florian, Vapalahti, Olli, Otto, Markus, Bartenschlager, Ralf, Herbeuval, Jean-Philippe, Schmidt-Chanasit, Jonas, Roan, Nadia R, and Münch, Jan

Subjects
Genitalia, Cell Line, Tumor, Vero Cells, Fibroblasts, Semen, Animals, Cercopithecus aethiops, Humans, Sexually Transmitted Diseases, Viral, RNA, Viral, Viral Load, Inhibitory Concentration 50, Virus Replication, Female, Male, Virus Attachment, Primary Cell Culture, Healthy Volunteers, Extracellular Vesicles, Zika Virus, Zika Virus Infection, Chlorocebus aethiops, Cell Line, Tumor, RNA, Viral, Sexually Transmitted Diseases
Abstract

Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse. Semen from ZIKV-infected individuals contains high viral loads and may therefore serve as an important vector for virus transmission. Here we analyze the effect of semen on ZIKV infection of cells and tissues derived from the anogenital region. ZIKV replicates in all analyzed cell lines, primary cells, and endometrial or vaginal tissues. However, in the presence of semen, infection by ZIKV and other flaviviruses is potently inhibited. We show that semen prevents ZIKV attachment to target cells, and that an extracellular vesicle preparation from semen is responsible for this anti-ZIKV activity. Our findings suggest that ZIKV transmission is limited by semen. As such, semen appears to serve as a protector against sexual ZIKV transmission, despite the availability of highly susceptible cells in the anogenital tract and high viral loads in this bodily fluid.

Published
2018

32. The molecular tweezer CLR01 inhibits Ebola and Zika virus infection

Author

Röcker, Annika E, Müller, Janis A, Dietzel, Erik, Harms, Mirja, Krüger, Franziska, Heid, Christian, Sowislok, Andrea, Riber, Camilla Frich, Kupke, Alexandra, Lippold, Sina, von Einem, Jens, Beer, Judith, Knöll, Bernd, Becker, Stephan, Schmidt-Chanasit, Jonas, Otto, Markus, Vapalahti, Olli, Zelikin, Alexander N, Bitan, Gal, Schrader, Thomas, and Münch, Jan

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Infectious Diseases, Vaccine Related, Prevention, Emerging Infectious Diseases, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Animals, Antiviral Agents, Bridged-Ring Compounds, Cell Line, Chlorocebus aethiops, Ebolavirus, Hemorrhagic Fever, Ebola, Humans, Organophosphates, Vero Cells, Virus Replication, Zika Virus, Zika Virus Infection, Zika virus, Ebola virus, Broadly active antiviral agents, Virus inactivation, Lipid rafts, Microbiology, Pharmacology and Pharmaceutical Sciences, Virology, Medical microbiology, Pharmacology and pharmaceutical sciences
Abstract

Ebola (EBOV) and Zika viruses (ZIKV) are responsible for recent global health threats. As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. This small molecule has previously been shown to inactivate HIV-1 and herpes viruses through a selective interaction with lipid-raft-rich regions in the viral envelope, which results in membrane disruption and loss of infectivity. We found that CLR01 indeed blocked infection of EBOV and ZIKV in a dose-dependent manner. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Our findings show that CLR01 is a broad-spectrum inhibitor of enveloped viruses with prospects as a preventative microbicide or antiviral agent.

Published
2018

34. Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants

Author

Belik, Milja, Jalkanen, Pinja, Lundberg, Rickard, Reinholm, Arttu, Laine, Larissa, Väisänen, Elina, Skön, Marika, Tähtinen, Paula A., Ivaska, Lauri, Pakkanen, Sari H., Häkkinen, Hanni K., Ortamo, Eeva, Pasternack, Arja, Ritvos, Mikael A., Naves, Rauno A., Miettinen, Simo, Sironen, Tarja, Vapalahti, Olli, Ritvos, Olli, Österlund, Pamela, Kantele, Anu, Lempainen, Johanna, Kakkola, Laura, Kolehmainen, Pekka, and Julkunen, Ilkka

Published
2022
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37. Incidence Trends for SARS-CoV-2 Alpha and Beta Variants, Finland, Spring 2021

Author

Kant, Ravi, Nguyen, Phuoc Truong, Blomqvist, Soile, Erdin, Mert, Alburkat, Hussein, Suvanto, Maija, Zakham, Fathiah, Salminen, Veera, Olander, Viktor, Paloniemi, Minna, Huhti, Leena, Lehtinen, Sara, Luukinen, Bruno, Jarva, Hanna, Kallio-Kokko, Hannimari, Kurkela, Satu, Lappalainen, Maija, Liimatainen, Hanna, Hannula, Sari, Halkilahti, Jani, Ikonen, Jonna, Ikonen, Niina, Helve, Otto, Gunell, Marianne, Vuorinen, Tytti, Plyusnin, Ilya, Lindh, Erika, Ellonen, Pekka, Sironen, Tarja, Savolainen-Kopra, Carita, Smura, Teemu, and Vapalahti, Olli

Subjects
Statistics, Identification and classification, Genetic aspects, Causes of, Forecasts and trends, Market trend/market analysis, SARS-CoV-2 variants -- Statistics -- Identification and classification -- Genetic aspects, Epidemics -- Statistics -- Causes of -- Forecasts and trends -- Finland, COVID-19 -- Statistics -- Causes of -- Forecasts and trends
Abstract

Several new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged globally, most notably variants of concern Alpha (B.1.1.7) (1), Beta (B1.351) (2), Gamma (P.1) (3), and most [...]

Published
2021
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40. Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

Author

Lin, Jing-wen, Tang, Chao, Wei, Han-cheng, Du, Baowen, Chen, Chuan, Wang, Minjin, Zhou, Yongzhao, Yu, Ming-xia, Cheng, Lu, Kuivanen, Suvi, Ogando, Natacha S., Levanov, Lev, Zhao, Yuancun, Li, Chang-ling, Zhou, Ran, Li, Zhidan, Zhang, Yiming, Sun, Ke, Wang, Chengdi, Chen, Li, Xiao, Xia, Zheng, Xiuran, Chen, Sha-sha, Zhou, Zhen, Yang, Ruirui, Zhang, Dan, Xu, Mengying, Song, Junwei, Wang, Danrui, Li, Yupeng, Lei, ShiKun, Zeng, Wanqin, Yang, Qingxin, He, Ping, Zhang, Yaoyao, Zhou, Lifang, Cao, Ling, Luo, Feng, Liu, Huayi, Wang, Liping, Ye, Fei, Zhang, Ming, Li, Mengjiao, Fan, Wei, Li, Xinqiong, Li, Kaiju, Ke, Bowen, Xu, Jiannan, Yang, Huiping, He, Shusen, Pan, Ming, Yan, Yichen, Zha, Yi, Jiang, Lingyu, Yu, Changxiu, Liu, Yingfen, Xu, Zhiyong, Li, Qingfeng, Jiang, Yongmei, Sun, Jiufeng, Hong, Wei, Wei, Hongping, Lu, Guangwen, Vapalahti, Olli, Luo, Yunzi, Wei, Yuquan, Connor, Thomas, Tan, Wenjie, Snijder, Eric J., Smura, Teemu, Li, Weimin, Geng, Jia, Ying, Binwu, and Chen, Lu

Published
2021
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43. Experimental Infection of Mink with SARS-COV-2 Omicron Variant and Subsequent Clinical Disease

Author

Virtanen, Jenni, Aaltonen, Kirsi, Kegler, Kristel, Venkat, Vinaya, Niamsap, Thanakorn, Kareinen, Lauri, Malmgren, Rasmus, Kivela, Olga, Atanasova, Nina, Osterlund, Pamela, Smura, Teemu, Sukura, Antti, Strandin, Tomas, Dutra, Lara, Vapalahti, Olli, Nordgren, Heli, Kant, Ravi, and Sironen, Tarja

Subjects
Development and progression, Research, Risk factors, Health aspects, Disease transmission -- Research, SARS-CoV-2 variants -- Research, Medical research, American mink -- Health aspects, COVID-19 -- Risk factors -- Development and progression, Medicine, Experimental
Abstract

SARS-CoV-2 has been detected in farmed and feral American mink (Neovison vison) in multiple countries, and extensive environmental contamination and human-to-mink and mink-to-human transmission has been documented (1-5). These factors [...]

Published
2022

44. Dynamin independent endocytosis is an alternative cell entry mechanism for multiple animal viruses.

Author

Ojha, Ravi, Jiang, Anmin, Mäntylä, Elina, Quirin, Tania, Modhira, Naphak, Witte, Robert, Gaudin, Arnaud, De Zanetti, Lisa, Gormal, Rachel Sarah, Vihinen-Ranta, Maija, Mercer, Jason, Suomalainen, Maarit, Greber, Urs F., Yamauchi, Yohei, Lozach, Pierre-Yves, Helenius, Ari, Vapalahti, Olli, Young, Paul, Watterson, Daniel, and Meunier, Frédéric A.

Subjects
SARS-CoV-2, SARS-CoV-2 Omicron variant, PATHOGENIC viruses, VESICULAR stomatitis, ANGIOTENSIN converting enzyme
Abstract

Mammalian receptor-mediated endocytosis (RME) often involves at least one of three isoforms of the large GTPase dynamin (Dyn). Dyn pinches-off vesicles at the plasma membrane and mediates uptake of many viruses, although some viruses directly penetrate the plasma membrane. RME is classically interrogated by genetic and pharmacological interference, but this has been hampered by undesired effects. Here we studied virus entry in conditional genetic knock-out (KO) mouse embryonic fibroblasts lacking expression of all three dynamin isoforms (Dyn-KO-MEFs). The small canine parvovirus known to use a single receptor, transferrin receptor, strictly depended on dynamin. Larger viruses or viruses known to use multiple receptors, including alphaviruses, influenza, vesicular stomatitis, bunya, adeno, vaccinia, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and rhinoviruses infected Dyn-KO-MEFs, albeit at higher dosage than wild-type MEFs. In absence of the transmembrane protease serine subtype 2 (TMPRSS2), which normally activates the SARS-CoV-2 spike protein for plasma membrane fusion, SARS-CoV-2 infected angiotensin-converting enzyme 2 (ACE2)-expressing MEFs predominantly through dynamin- and actin-dependent endocytosis. In presence of TMPRSS2 the ancestral Wuhan-strain bypassed both dynamin-dependent and -independent endocytosis, and was less sensitive to endosome maturation inhibitors than the Omicron B1 and XBB variants, supporting the notion that the Omicron variants do not efficiently use TMPRSS2. Collectively, our study suggests that dynamin function at endocytic pits can be essential for infection with single-receptor viruses, while it is not essential but increases uptake and infection efficiency of multi-receptor viruses that otherwise rely on a functional actin network for infection. Author summary: To initiate their infection cycle, most viruses first need to enter their target cells, a process called endocytosis. In mammalian cells, endocytosis often involves a class of proteins called dynamins. While numerous viruses, including SARS-CoV-2, efficiently infect cells by dynamin-mediated endocytosis we found that in the absence of these proteins an alternative cell entry mechanism exists, allowing multiple pathogenic human viruses to enter and infect cells. Unlike the dynamin-mediated infection, the efficient internalization of viral particles via dynamin-independent endocytosis seems to always require functional actin fibers, which are structural components of the cell contractile cytoskeleton. Thus, multiple viruses can infect their target cells using at last two entry mechanisms, inhibiting both may provide effective antiviral therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Circulating mucosal-like IgA responses increase with severity of Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome.

Author

Cabrera, Luz E., Buckner, Cienna, Then, Veronica, Mäki, Sanna, Vapalahti, Olli, Vaheri, Antti, Hepojoki, Jussi, Tietäväinen, Johanna, Mäkelä, Satu, Mustonen, Jukka, and Strandin, Tomas

Subjects
HEMORRHAGIC fever with renal syndrome, IMMUNE response, ACUTE kidney failure, IMMUNOGLOBULIN A, IMMUNE system
Abstract

Old World Orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) characterized by increased vascular permeability and acute kidney injury (AKI). Despite the systemic nature of the disease, the virus enters humans through inhalation and therefore initially encounters the immunoglobulin class A (IgA) dominated mucosal immune system. Herein, we characterized systemic IgA responses and their potential relationship to the mucosal immune activation by examining blood samples obtained from patients hospitalized due to acute Puumala orthohantavirus infection. Our findings reveal increased frequencies of putative IgA-expressing circulating mucosal-associated B1 cells and plasmablasts, as well as elevated levels of polyreactive, polymeric, virus-specific and secretory IgA in the acute stage of the disease. Importantly, the levels of circulating virus-specific and secretory IgA, as well as the putative IgA+ B1 cells, increased with the severity of AKI. Furthermore, circulating polymeric IgA displayed enhanced effector functions by forming stable complexes with the IgA receptor CD89 and induced pro-inflammatory neutrophil responses. These results suggest that excessive levels of circulating mucosal-like IgA might serve as a biomarker for HFRS disease progression. [ABSTRACT FROM AUTHOR]

Published
2024
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47. Systems-Level Immunomonitoring from Acute to Recovery Phase of Severe COVID-19

Author

Rodriguez, Lucie, Pekkarinen, Pirkka T., Lakshmikanth, Tadepally, Tan, Ziyang, Consiglio, Camila Rosat, Pou, Christian, Chen, Yang, Mugabo, Constantin Habimana, Nguyen, Ngoc Anh, Nowlan, Kirsten, Strandin, Tomas, Levanov, Lev, Mikes, Jaromir, Wang, Jun, Kantele, Anu, Hepojoki, Jussi, Vapalahti, Olli, Heinonen, Santtu, Kekäläinen, Eliisa, and Brodin, Petter

Published
2020
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50. Lymphocytic Choriomeningitis Virus Infections and Seroprevalence, Southern Iraq

Author

Alburkat, Hussein, Jaaskelainen, Anne J., Barakat, Ali M., Hasony, Hassan J., Sironen, Tarja, Al-hello, Haider, Smura, Teemu, and Vapalahti, Olli

Subjects
Diagnosis, Statistics, Causes of, Viral meningitis -- Causes of -- Diagnosis -- Statistics
Abstract

Lymphocytic choriomeningitis virus (LCMV) is a rodentborne pathogen that belongs to the genus Mammarenavirus, family Arenaviridae. The house mouse (Mus musculus) is considered the reservoir of LCMV (1). Humans can [...]

Published
2020
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