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1. A low dose of RBD and TLR7/8 agonist displayed on influenza virosome particles protects rhesus macaque against SARS-CoV-2 challenge

Author

Koopman, Gerrit, Amacker, Mario, Stegmann, Toon, Verschoor, Ernst J., Verstrepen, Babs E., Bhoelan, Farien, Bemelman, Denzel, Böszörményi, Kinga P., Fagrouch, Zahra, Kiemenyi-Kayere, Gwendoline, Mortier, Daniella, Verel, Dagmar E., Niphuis, Henk, Acar, Roja Fidel, Kondova, Ivanela, Kap, Yolanda S., Bogers, Willy M. J. M., Mooij, Petra, and Fleury, Sylvain

Published
2023
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3. SARS-CoV-2 in lions, gorillas and zookeepers in the Rotterdam Zoo, the Netherlands, a One Health investigation, November 2021

Author

Dusseldorp, Florien, primary, Bruins-van-Sonsbeek, Linda G.R., additional, Buskermolen, Maaike, additional, Niphuis, Henk, additional, Dirven, Mariëlle, additional, Whelan, Jane, additional, Oude Munnink, Bas B., additional, Koopmans, Marion, additional, Fanoy, Ewout B., additional, Sikkema, Reina S., additional, and Tjon-A-Tsien, Aimée, additional

Published
2023
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4. SARS-CoV-2 in lions, gorillas and zookeepers in the Rotterdam Zoo, the Netherlands, a One Health investigation, November 2021

Author

Dusseldorp, Florien, Bruins-van-Sonsbeek, Linda G.R., Buskermolen, Maaike, Niphuis, Henk, Dirven, Mariëlle, Whelan, Jane, Oude Munnink, Bas B., Koopmans, Marion, Fanoy, Ewout B., Sikkema, Reina S., Tjon-A-Tsien, Aimée, Dusseldorp, Florien, Bruins-van-Sonsbeek, Linda G.R., Buskermolen, Maaike, Niphuis, Henk, Dirven, Mariëlle, Whelan, Jane, Oude Munnink, Bas B., Koopmans, Marion, Fanoy, Ewout B., Sikkema, Reina S., and Tjon-A-Tsien, Aimée

Abstract

In November 2021, seven western lowland gorillas and four Asiatic lions were diagnosed with COVID-19 at Rotterdam Zoo. An outbreak investigation was undertaken to determine the source and extent of the outbreak and to identify possible transmission routes. Interviews were conducted with staff to identify human and animal contacts and cases, compliance with personal protective equipment (PPE) and potential transmission routes. Human and animal contacts and other animal species suspected to be susceptible to SARS-CoV-2 were tested for SARS-CoV-2 RNA. Positive samples were subjected to sequencing. All the gorillas and lions that could be tested (3/7 and 2/4, respectively) were RT-PCR positive between 12 November and 10 December 2021. No other animal species were SARS-CoV-2 RNA positive. Forty direct and indirect human contacts were identified. Two direct contacts tested RT-PCR positive 10 days after the first COVID-19 symptoms in animals. The zookeepers' viral genome sequences clustered with those of gorillas and lions. Personal protective equipment compliance was suboptimal at instances. Findings confirm transmission of SARS-CoV-2 among animals and between humans and animals but source and directionality could not be established. Zookeepers were the most likely source and should have periodic PPE training. Sick animals should promptly be tested and isolated/quarantined.

Published
2023

5. Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2

Author

Mooij, Petra, García-Arriaza, Juan, Pérez, Patricia, Lázaro-Frías, Adrian, Verstrepen, Babs E., Böszörményi, Kinga P., Mortier, Daniella, Fagrouch, Zahra, Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Acar, Roja Fidel, Meijer, Lisette, Stammes, Marieke A., Kondova, Ivanela, Verschoor, Ernst J., GeurtsvanKessel, Corine H., de Bruin, Erwin, Sikkema, Reina S., Luczkowiak, Joanna, Delgado, Rafael, Montenegro, Dolores, Puentes, Eugenia, Rodríguez, Esteban, Bogers, Willy M. J. M., Koopman, Gerrit, Esteban, Mariano, Ministerio de Sanidad (España), Instituto de Salud Carlos III, Banco Santander, Conferencia de Rectores de las Universidades Españolas, Consejo Superior de Investigaciones Científicas (España), Fundación 'la Caixa', Ferrovial, Fundación Mapfre, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Biomedical Primate Research Centre (The Netherlands), European Commission, and Virology

Subjects
COVID-19 Vaccines, Rhesus macaques, Efficacy, SARS-CoV-2, viruses, Immunology, COVID-19, Vaccinia virus, Spike, respiratory system, Antibodies, Viral, Macaca mulatta, complex mixtures, Immunogenicity, respiratory tract diseases, SDG 3 - Good Health and Well-being, Spike Glycoprotein, Coronavirus, Immunology and Allergy, Animals, Humans, Safety, MVA vaccine, Pandemics
Abstract

Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was well tolerated and induced S and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against SARS-CoV-2 and several variants of concern. S-specific IFNγ, but not IL-4, -producing cells were also elicited. After SARS-CoV-2 challenge, vaccinated animals showed a significant strong reduction of virus loads in bronchoalveolar lavages (BAL) and decreased levels in throat and nasal mucosa. Remarkably, MVA-S also protected macaques from fever and infection-induced cytokine storm. Computed tomography and histological examination of the lungs showed reduced lung pathology in MVA-S-vaccinated animals. These findings favor the use of MVA-S as a potential vaccine for SARS-CoV-2 in clinical trials., This research was supported by Fondo COVID-19 grant COV20/00151 (Spanish Health Ministry, Instituto de Salud Carlos III (ISCIII)), Fondo Supera COVID-19 grant (Crue Universidades-Banco Santander), and Spanish Research Council (CSIC) grant 202120E079 (to JG-A); CSIC grant 2020E84, la Caixa Banking Foundation grant CF01-00008, Ferrovial, and MAPFRE donations (to ME); a Spanish Ministry of Science and Innovation (MCIN)/Spanish Research Agency (AEI)/10.13039/501100011033 grant (PID2020-114481RB-I00; to JG-A and ME); and internal funding from the BPRC. This research work was also funded by the European Commission-NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global) (to JG-A and ME). RD received grants from the European Commission Horizon 2020 Framework Programme (Project VIRUSCAN FETPROACT-2016: 731868 and Project EPIC-CROWN-2: 101046084), and Fundación Caixa-Health Research HR18-00469 (Project StopEbola).

Published
2022

7. The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Author

Böszörményi, Kinga, Stammes, Marieke, Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, Driel, Nikki van, Nieuwenhuis, Ivonne, Vervenne, Richard A. W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Hoste, Alexis C. R., Sastre, Patricia, Haagmans, Bart, Bontrop, Ronald E., Langermans, Jan, Bogers, Willy, Kondova, Ivanela, Verschoor, Ernst, Verstrepen, Babs E, Sub Theoretical Biology, AISS LAS/3'R Centre ULS, and Theoretical Biology and Bioinformatics

Subjects
NHPs, Infectious Diseases, SARS-CoV-2, Virology, COVID-19, Animal models, Non-human primates
Abstract

The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.

Published
2021

9. The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Author

Böszörményi, Kinga P., primary, Stammes, Marieke A., additional, Fagrouch, Zahra C., additional, Kiemenyi-Kayere, Gwendoline, additional, Niphuis, Henk, additional, Mortier, Daniella, additional, van Driel, Nikki, additional, Nieuwenhuis, Ivonne, additional, Vervenne, Richard A. W., additional, Haaksma, Tom, additional, Ouwerling, Boudewijn, additional, Adema, Deborah, additional, Acar, Roja Fidel, additional, Zuiderwijk-Sick, Ella, additional, Meijer, Lisette, additional, Mooij, Petra, additional, Remarque, Ed J., additional, Oostermeijer, Herman, additional, Koopman, Gerrit, additional, Hoste, Alexis C. R., additional, Sastre, Patricia, additional, Haagmans, Bart L., additional, Bontrop, Ronald E., additional, Langermans, Jan A. M., additional, Bogers, Willy M., additional, Kondova, Ivanela, additional, Verschoor, Ernst J., additional, and Verstrepen, Babs E., additional

Published
2021
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10. The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Author

Sub Theoretical Biology, AISS LAS/3'R Centre ULS, Theoretical Biology and Bioinformatics, Böszörményi, Kinga, Stammes, Marieke, Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, Driel, Nikki van, Nieuwenhuis, Ivonne, Vervenne, Richard A. W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Hoste, Alexis C. R., Sastre, Patricia, Haagmans, Bart, Bontrop, Ronald E., Langermans, Jan, Bogers, Willy, Kondova, Ivanela, Verschoor, Ernst, Verstrepen, Babs E, Sub Theoretical Biology, AISS LAS/3'R Centre ULS, Theoretical Biology and Bioinformatics, Böszörményi, Kinga, Stammes, Marieke, Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, Driel, Nikki van, Nieuwenhuis, Ivonne, Vervenne, Richard A. W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Hoste, Alexis C. R., Sastre, Patricia, Haagmans, Bart, Bontrop, Ronald E., Langermans, Jan, Bogers, Willy, Kondova, Ivanela, Verschoor, Ernst, and Verstrepen, Babs E

Published
2021

11. The post-acute phase of sars-cov-2 infection in two macaque species is associated with signs of ongoing virus replication and pathology in pulmonary and extrapulmonary tissues

Author

Böszörményi, Kinga P., Stammes, Marieke A., Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, van Driel, Nikki, Nieuwenhuis, Ivonne, Vervenne, Richard A.W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Koopman, Gerrit, Hoste, Alexis C.R., Sastre, Patricia, Haagmans, Bart L., Bontrop, Ronald E., Langermans, Jan A.M., Bogers, Willy M., Kondova, Ivanela, Verschoor, Ernst J., Verstrepen, Babs E., Böszörményi, Kinga P., Stammes, Marieke A., Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, van Driel, Nikki, Nieuwenhuis, Ivonne, Vervenne, Richard A.W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Koopman, Gerrit, Hoste, Alexis C.R., Sastre, Patricia, Haagmans, Bart L., Bontrop, Ronald E., Langermans, Jan A.M., Bogers, Willy M., Kondova, Ivanela, Verschoor, Ernst J., and Verstrepen, Babs E.

Abstract

The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.

Published
2021

15. Detection and characterization of two chimpanzee polyomavirus genotypes from different subspecies

Author

Niphuis Henk, Groenewoud Marlous J, Fagrouch Zahra, Deuzing Ilona, Kondova Ivanela, Bogers Willy, and Verschoor Ernst J

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract The complete nucleotide sequences of three chimpanzee polyomavirus genetic variants were determined. Phylogenetic analysis indicated that the viruses form two different genotypes of ChPyV. Comparison with other primate polyomaviruses revealed a putative agnogene, and an unusually long VP1 open reading frame. The transcriptional control regions (TCR) of the viruses were extremely short (155 nucleotides), and highly conserved amongst the genotypes. Analysis of the TCR from different chimpanzee subspecies, and from a series of tissues from five individuals confirmed its genetic stability, and also indicates that double-infections with different genotypes can occur.

Published
2010
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16. Human Herpesvirus 7 with Roseoloviruses Closely Related to African Great Apes Are Naturally Infected Supplemental material

Author

Lavergne, Anne, Donato, Damien, Gessain, Antoine, Niphuis, Henk, Nerrienet, Eric, Verschoor, Ernst J, Lacoste, Vincent, Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Biomedical Primate Research Centre [Rijswijk] (BPRC), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), This study benefited from European commission grant REGPOT-CT-2011-285837-STRonGer within the FP7 program, European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]

Subjects
MESH: Sequence Analysis, DNA, MESH: Molecular Sequence Data, viruses, MESH: DNA, Viral/chemistry, MESH: Roseolovirus/isolation & purification, MESH: Polymerase Chain Reaction, MESH: Africa, MESH: Roseolovirus/classification, MESH: Primate Diseases/virology, MESH: Cluster Analysis, MESH: Roseolovirus Infections/virology, MESH: Blood/virology, MESH: Genotype, MESH: Viral Proteins/genetics, MESH: Hominidae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Roseolovirus Infections/veterinary, MESH: DNA, Viral/genetics, MESH: Animals, MESH: Roseolovirus/genetics, MESH: Sequence Homology, MESH: Phylogeny
Abstract

International audience; Primates are naturally infected with herpesviruses. During the last 15 years, the search for homologues of human herpesvirusesin nonhuman primates allowed the identification of numerous viruses belonging to the different herpesvirus subfamilies andgenera. No simian homologue of human herpesvirus 7 (HHV7) has been reported to date. To investigate the putative existence ofHHV7-like viruses in African great apes, we applied the consensus-degenerate hybrid oligonucleotide primers (CODEHOP) program-mediated PCR strategy to blood DNA samples from the four common chimpanzee subspecies (Pan troglodytes verus, P. t.ellioti, P. t. troglodytes, and P. t. schweinfurthii), pygmy chimpanzees (Pan paniscus), as well as lowland gorillas (Gorilla gorillagorilla). This study led to the discovery of a novel roseolovirus close to HHV7 in each of these nonhuman primate species andsubspecies. Generation of the partial glycoprotein B (1,111-bp) and full-length DNA polymerase (3,036/3,042-bp) gene sequencesallowed the deciphering of their evolutionary relationships. Phylogenetic analyses revealed that HHV7 and its Africangreat ape homologues formed well-supported monophyletic lineages whose topological resemblance to the host phylogeny issuggestive of virus-host codivergence. Notably, the evolutionary branching points that separate HHV7 from African great apeherpesvirus 7 are remarkably congruent with the dates of divergence of their hosts. Our study shows that African great apes arehosts of human herpesvirus homologues, including HHV7 homologues, and that the latter, like other DNA viruses that establishpersistent infections, have cospeciated with their hosts.

Published
2014
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17. Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections

Author

Greenwood, Edward J. D., primary, Schmidt, Fabian, additional, Kondova, Ivanela, additional, Niphuis, Henk, additional, Hodara, Vida L., additional, Clissold, Leah, additional, McLay, Kirsten, additional, Guerra, Bernadette, additional, Redrobe, Sharon, additional, Giavedoni, Luis D., additional, Lanford, Robert E., additional, Murthy, Krishna K., additional, Rouet, François, additional, and Heeney, Jonathan L., additional

Published
2015
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19. Vaccine-Induced Protection of Rhesus Macaques against Plasma Viremia after Intradermal Infection with a European Lineage 1 Strain of West Nile Virus

Author

Verstrepen, Babs E., primary, Oostermeijer, Herman, additional, Fagrouch, Zahra, additional, van Heteren, Melanie, additional, Niphuis, Henk, additional, Haaksma, Tom, additional, Kondova, Ivanela, additional, Bogers, Willy M., additional, de Filette, Marina, additional, Sanders, Niek, additional, Stertman, Linda, additional, Magnusson, Sofia, additional, Lőrincz, Orsolya, additional, Lisziewicz, Julianna, additional, Barzon, Luisa, additional, Palù, Giorgio, additional, Diamond, Michael S., additional, Chabierski, Stefan, additional, Ulbert, Sebastian, additional, and Verschoor, Ernst J., additional

Published
2014
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22. A vaccine strategy utilizing a combination of three different chimeric vectors which share specific vaccine antigens

Author

Heeney, Jonathan L., Koopmans, Gerrit, Rosenwirth, Brigitte, Bogers, Willy, Van Dijk, Jeanette, Nieuwenhuis, Ivonne, Niphuis, Henk, Ten Haaft, Peter, Hanke, Thomas, Rhodes, Gary, Berglund, Peter, Burny, Arsène, Bex, Françoise, Sutter, Gerd, Liljeström, P, Heeney, Jonathan L., Koopmans, Gerrit, Rosenwirth, Brigitte, Bogers, Willy, Van Dijk, Jeanette, Nieuwenhuis, Ivonne, Niphuis, Henk, Ten Haaft, Peter, Hanke, Thomas, Rhodes, Gary, Berglund, Peter, Burny, Arsène, Bex, Françoise, Sutter, Gerd, and Liljeström, P

Abstract

SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Published
2000

23. Transmission of Simian Immunodeficiency Virus SIVcpz and the Evolution of Infection in the Presence and Absence of Concurrent Human Immunodeficiency Virus Type 1 Infection in Chimpanzees

Author

Heeney, Jonathan L., primary, Rutjens, Erik, additional, Verschoor, Ernst J., additional, Niphuis, Henk, additional, ten Haaft, Peter, additional, Rouse, Scott, additional, McClure, Hazel, additional, Balla-Jhagjhoorsingh, Sunita, additional, Bogers, Willy, additional, Salas, Mary, additional, Cobb, Kathy, additional, Kestens, Luc, additional, Davis, David, additional, van der Groen, Guido, additional, Courgnaud, Valerie, additional, Peeters, Martine, additional, and Murthy, Krishna K., additional

Published
2006
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26. Vaccine protection from CD4+ T-cell loss caused by simian immunodeficiency virus (SIV) mac251 is afforded by sequential immunization with three unrelated vaccine vectors encoding multiple SIV antigens

Author

Koopman, Gerrit, primary, Mortier, Daniella, additional, Hofman, Sam, additional, Niphuis, Henk, additional, Fagrouch, Zahra, additional, Norley, Steve, additional, Sutter, Gerd, additional, Liljeström, Peter, additional, and Heeney, Jonathan L., additional

Published
2004
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27. Qualitative T-Helper Responses to Multiple Viral Antigens Correlate with Vaccine-Induced Immunity to Simian/Human Immunodeficiency Virus Infection

Author

Mooij, Petra, primary, Nieuwenhuis, Ivonne G., additional, Knoop, Christiaan J., additional, Doms, Robert W., additional, Bogers, Willy M. J. M., additional, ten Haaft, Peter J. F., additional, Niphuis, Henk, additional, Koornstra, Wim, additional, Bieler, Kurt, additional, Köstler, Josef, additional, Morein, Brør, additional, Cafaro, Aurelio, additional, Ensoli, Barbara, additional, Wagner, Ralf, additional, and Heeney, Jonathan L., additional

Published
2004
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30. Characteristics of a Pathogenic Molecular Clone of an End-Stage Serum-Derived Variant of Simian Immunodeficiency Virus (SIV F359 )

Author

Holterman, Lennart, primary, Dubbes, Rob, additional, Mullins, James, additional, Learn, Gerald, additional, Niphuis, Henk, additional, Koornstra, Wim, additional, Koopman, Gerrit, additional, Kuhn, Eva-Maria, additional, Wade-Evans, Alison, additional, Rosenwirth, Brigitte, additional, Haaijman, Joost, additional, and Heeney, Jonathan, additional

Published
2001
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32. Herpesvirus Saimiri vFLIP Provides an Antiapoptotic Function but Is Not Essential for Viral Replication, Transformation, or Pathogenicity

Author

Glykofrydes, Diana, primary, Niphuis, Henk, additional, Kuhn, Eva M., additional, Rosenwirth, Brigitte, additional, Heeney, Jonathan L., additional, Bruder, Joseph, additional, Niedobitek, Gerald, additional, Müller-Fleckenstein, Ingrid, additional, Fleckenstein, Bernhard, additional, and Ensser, Armin, additional

Published
2000
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34. Antiretroviral Therapy during Primary Immunodeficiency Virus Infection Can Induce Persistent Suppression of Virus Load and Protection from Heterologous Challenge in Rhesus Macaques

Author

Rosenwirth, Brigitte, primary, ten Haaft, Peter, additional, Bogers, Willy M. J. M., additional, Nieuwenhuis, Ivonne G., additional, Niphuis, Henk, additional, Kuhn, Eva-Maria, additional, Bischofberger, Norbert, additional, Heeney, Jonathan L., additional, and Überla, Klaus, additional

Published
2000
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36. The Interleukin-17 Gene of Herpesvirus Saimiri

Author

Knappe, Andrea, primary, Hiller, Christian, additional, Niphuis, Henk, additional, Fossiez, François, additional, Thurau, Mathias, additional, Wittmann, Sabine, additional, Kuhn, Eva-Maria, additional, Lebecque, Serge, additional, Banchereau, Jacques, additional, Rosenwirth, Brigitte, additional, Fleckenstein, Bernhard, additional, Heeney, Jonathan, additional, and Fickenscher, Helmut, additional

Published
1998
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39. Comparison ofin Vitroandin VivoInfectivity of Different Clade B HIV-1 Envelope Chimeric Simian/Human Immunodeficiency Viruses inMacaca mulatta

Author

Bogers, Willy M.J.M, primary, Dubbes, Rob, additional, ten Haaft, Peter, additional, Niphuis, Henk, additional, Cheng-Mayer, Cecilia, additional, Stahl-Hennig, Christiane, additional, Hunsmann, Gerhard, additional, Kuwata, Takeo, additional, Hayami, Masanori, additional, Jones, Sue, additional, Ranjbar, Shahin, additional, Almond, Neil, additional, Stott, Jim, additional, Rosenwirth, Brigitte, additional, and Heeney, Jonathan L, additional

Published
1997
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40. Molecular Analysis of a Novel Simian Virus 40 (SV40) Type in Rhesus Macaques and Evidence for Double Infections with the Classical SV40 Type

Author

Fagrouch, Zahra, Karremans, Kevin, Deuzing, Ilona, van Gessel, Sabine, Niphuis, Henk, Bogers, Willy, and Verschoor, Ernst J.

Abstract

ABSTRACTThe incidence of simian virus 40 (SV40) infections in rhesus macaques infected with simian-human immunodeficiency viruses (SHIV) and in uninfected animals was determined using PCR. Rates varied from 5% in peripheral blood mononuclear cells of uninfected monkeys to 19.6% in SHIV-infected macaques. Much higher detection rates, up to 75%, were found in lymph nodes and spleen samples of SHIV-infected animals. Sequence analysis of PCR amplicons revealed that they form two genetic clusters, one containing the majority of known SV40 strains and the other formed by variants with 7% genetic difference. Based on this difference, we propose two SV40 types: “type 1” or “classical type” for the majority of SV40 strains and “type 2” for the novel SV40 variants. The genome of one variant, SV40-Ri257, was completely sequenced and analyzed. The agnogene of SV40-Ri257 extends into the VP2 open reading frame and encodes a typical agnoprotein fused to a C-terminal hydrophobic region. The transcriptional control region (TCR) of SV40-Ri257 is the least conserved region compared to type 1 viruses. Particularly, the 3' end of the TCR, containing the early promoter and enhancer region, exhibits considerable variation. Further analysis of SHIV-infected macaques with type-specific PCRs revealed that the TCR of type 1 was completely conserved, whereas this region in type 2 varied considerably within the early enhancer region. We provide evidence here for the existence of a novel SV40 type in rhesus macaques and show that double infections with both types frequently occur.

Published
2011
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41. Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2.

Author

Mooij P, García-Arriaza J, Pérez P, Lázaro-Frías A, Verstrepen BE, Böszörményi KP, Mortier D, Fagrouch Z, Kiemenyi-Kayere G, Niphuis H, Acar RF, Meijer L, Stammes MA, Kondova I, Verschoor EJ, GeurtsvanKessel CH, de Bruin E, Sikkema RS, Luczkowiak J, Delgado R, Montenegro D, Puentes E, Rodríguez E, Bogers WMJM, Koopman G, and Esteban M

Subjects
Animals, Antibodies, Viral, COVID-19 Vaccines, Humans, Macaca mulatta, Pandemics, SARS-CoV-2 genetics, Spike Glycoprotein, Coronavirus, COVID-19 prevention & control, Vaccinia virus genetics
Abstract

Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was well tolerated and induced S and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against SARS-CoV-2 and several variants of concern. S-specific IFNγ, but not IL-4, -producing cells were also elicited. After SARS-CoV-2 challenge, vaccinated animals showed a significant strong reduction of virus loads in bronchoalveolar lavages (BAL) and decreased levels in throat and nasal mucosa. Remarkably, MVA-S also protected macaques from fever and infection-induced cytokine storm. Computed tomography and histological examination of the lungs showed reduced lung pathology in MVA-S-vaccinated animals. These findings favor the use of MVA-S as a potential vaccine for SARS-CoV-2 in clinical trials., Competing Interests: Author EP was employed by Biofabri. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mooij, García-Arriaza, Pérez, Lázaro-Frías, Verstrepen, Böszörményi, Mortier, Fagrouch, Kiemenyi-Kayere, Niphuis, Acar, Meijer, Stammes, Kondova, Verschoor, GeurtsvanKessel, de Bruin, Sikkema, Luczkowiak, Delgado, Montenegro, Puentes, Rodríguez, Bogers, Koopman and Esteban.)

Published
2022
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42. Characterization of novel polyomaviruses from Bornean and Sumatran orang-utans.

Author

Groenewoud MJ, Fagrouch Z, van Gessel S, Niphuis H, Bulavaite A, Warren KS, Heeney JL, and Verschoor EJ

Subjects
Amino Acid Sequence, Animals, Borneo, Cluster Analysis, DNA, Viral chemistry, DNA, Viral genetics, Gene Order, Genes, Viral, Indonesia, Molecular Sequence Data, Phylogeny, Polymerase Chain Reaction methods, Polyomavirus genetics, Polyomavirus Infections virology, Sequence Alignment, Sequence Analysis, DNA, Synteny, Tumor Virus Infections virology, Ape Diseases virology, Polyomavirus classification, Polyomavirus isolation & purification, Polyomavirus Infections veterinary, Pongo abelii virology, Pongo pygmaeus virology, Tumor Virus Infections veterinary
Abstract

Serological screening of sera from orang-utans demonstrated a high percentage of sera that cross-reacted with antigens of the polyomavirus (PyV) simian virus 40. Analysis of archival DNA samples from 71 Bornean and eight Sumatran orang-utans with a broad-spectrum PCR assay resulted in the detection of PyV infections in 11 animals from both species. Sequence analysis of the amplicons revealed considerable differences between the PyVs from Bornean and Sumatran orang-utans. The genome from two PyVs, one from each species, was therefore amplified and sequenced. Both viral genomes revealed a characteristic PyV architecture, but lacked an obvious agnogene. Neighbour-joining analysis positioned the viruses in a large cluster together with viruses from bats, bovines, rodents and several primate PyVs from chimpanzees, African green monkeys, squirrel monkeys and the human Merkel cell PyV.

Published
2010
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43. Specific passage of simian immunodeficiency virus from end-stage disease results in accelerated progression to AIDS in rhesus macaques.

Author

Holterman L, Niphuis H, Ten Haaft PJF, Goudsmit J, Baskin G, and Heeney JL

Subjects
Animals, Antigens, Viral blood, CD4-Positive T-Lymphocytes immunology, Disease Progression, Flow Cytometry, Immunologic Memory, Macaca mulatta, Male, RNA, Viral blood, Simian Acquired Immunodeficiency Syndrome immunology, Simian Immunodeficiency Virus physiology, Viral Load, Virulence, Simian Acquired Immunodeficiency Syndrome physiopathology, Simian Acquired Immunodeficiency Syndrome virology, Simian Immunodeficiency Virus pathogenicity
Abstract

To determine whether passage of late-stage variants of simian immunodeficiency virus (SIV) would lead to a more virulent infection and rapid disease progression, a study was designed to examine the effects of selective transmission of SIV from late-stage cases of AIDS in Macaca mulatta. In a uniform group of 10 age-matched animals from the same genetic breeding stock infected with SIV(B670), it took 7 months before one of the ten animals developed AIDS. Passage of virus taken from this animal immediately prior to death resulted in death of the recipient due to AIDS within 4 months. Again, subsequent passage of virus taken late in disease resulted in an accelerated disease course, with AIDS developing within 2.5 and 1.8 months in two recipients. The fourth passage of virus taken late in disease from the most rapid progressor (1.8 months) resulted in AIDS developing in this recipient within 1 month of infection. During each consecutive passage in vivo, the loss of memory T cells became more acute. Evidence that the virus became more virulent with selective passage of late-stage variants was provided by the markedly increased levels of both plasma antigen and viral RNA. Subsequent in vivo passage from end-stage AIDS selected for a strain of SIV capable of causing the acute development of AIDS as rapidly as 1 month post-infection. The pathology of acute AIDS in these cases closely resembled that seen after a chronic disease course.

Published
1999
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