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Koopmans, M. P. G.

Publications and source records attributed to Koopmans, M. P. G..

8 recordsLinked to original sources

Persistent circulation of Rift Valley fever virus lineage C in Rwanda, 2022-2025

Rwanda has experienced recurrent Rift Valley fever virus outbreaks in the last decade. In this study, we investigated whether these outbreaks resulted from repeated introductions or sustained local circulation. We generated RVFV whole-genome sequences from livestock samples collected between 2022 and 2025 using Nanopore sequencing. Genomic analyses indicated the outbreaks resulted from sustained local circulation of lineage C rather than repeated introductions, suggesting ongoing transmission likely driven by sporadic spillover. This study underscores the importance of continuous genomic surveillance in endemic settings.

genomics↗

Shared viral burdens: Evidence of active Usutu virus circulation and multi-arbovirus exposure in migrant and resident birds at wintering locations in Nigeria

BackgroundWest Nile (WNV), Usutu (USUV), and Sindbis (SINV) virus were initially detected in the African region, and subsequently across temperate regions where they were absent. Wild birds are primary reservoirs for these arboviruses and are considered major contributors to their global spread through seasonal migration. To understand the transmission dynamics of arboviruses in wild birds and the potential of migratory birds to spread the viruses at an intercontinental scale, we investigated arboviral infections and exposures in African resident and Palearctic migratory birds at wintering locations in Nigeria. Methodology/Principal FindingsOropharyngeal- and cloacal swabs, feathers and blood were collected from resident and migratory birds at two wintering locations (Amurum and Ngel-Nyaki Forest Reserves). Swabs and feathers were tested using RT-PCR for WNV, USUV and SINV, and blood with ELISA and FRNT90 or PRNT80 for antibodies. 573 birds were sampled between 2021 to 2024 across months coinciding with arrival and departure of migratory birds. USUV RNA was detected in 2.6% of feathers including a positive Icterine warbler and a garden warbler sampled prior to spring migration. None of the swabs was positive for viral RNA but neutralizing antibodies to WNV and USUV were detected in 4.5% of birds. SINV antibodies were also found in 34.1% of birds sampled across the wintering locations. Conclusions/SignificanceOur findings showed that migratory birds can become infected with USUV, and potentially with WNV and SINV during their overwintering periods in Africa and highlighted a wider arbovirus risk in Nigeria. In addition, detections of viral RNA in feathers, but not swabs, suggest feathers may be a suitable matrix for surveillance in the absence of a reliable cold chain. The overall detections in wild birds at these locations highlight the need for further surveillance to define the epidemiology and public health risks of these arboviruses in the region. SynopsisVector-borne viruses like West Nile, Usutu, and Sindbis, were once limited to parts of Africa, but now appear in Europe and other temperate regions. Migratory birds are believed to help spread these viruses across continents. To understand the role of birds in this, we tested resident and migratory birds in Nigeria for evidence of infection. Between 2021 and 2024, we sampled over 570 birds during their winter stay. We found genetic material of Usutu virus in feathers of six birds including two migratory birds just before their return to Europe. While swab tests did not detect active infections, antibodies to these viruses, which indicate past exposure, were found in several birds, especially for Sindbis virus. Our findings show that migratory birds can pick up and possibly carry these viruses across continents. We also found that feathers may be a practical tool for virus detection in areas without reliable refrigeration, supporting easier and broader surveillance of these viruses in Africa and possibly beyond.

microbiology↗

Emergence and Dynamics of Usutu and West Nile Viruses in the Netherlands, 2016-2022

BackgroundMosquito-borne arboviruses, including Usutu virus (USUV) and West Nile virus (WNV), are emerging threats in Europe, with changes in climate, land use, and increased travel and trade influencing their dynamics. Understanding the emergence and establishment of these viruses in new regions is critical for informing targeted mitigation of drivers of emergence and enhancing public and wildlife health preparedness. MethodsSeven years (2016-2022) of interconnected studies were conducted in the Netherlands. Live birds were sampled by volunteer bird ringers, dead birds were referred for sampling by citizen-scientists and zoological institutions, and mosquitoes were trapped. Samples were tested for USUV and WNV using RT-PCR and screened for Orthoflavivirus antibodies using protein microarray and neutralization assays. Sequencing and phylogenetic analyses were performed. FindingsUSUV was first detected in the Netherlands in 2016, caused large outbreaks in birds until 2018, and resurged in 2022. One dominant, enzootic lineage, co-circulated alongside several limited introductions of a second lineage. A localized WNV lineage 2 outbreak occurred in live birds and mosquitoes in 2020, with another positive bird in 2022 and serological evidence of continued circulation. InterpretationWe provide the first comprehensive, multi-year documentation of two emerging arboviruses in the Netherlands. USUV was enzootically maintained over seven years and was associated with substantial bird mortality. WNV is in an early stage of establishment with no bird mortality observed. Our integrated wildlife sampling was crucial in detecting a human WNV outbreak, bringing this emerging threat to public health attention. FundingZonMw, Dutch Research Council (NWO), European Union, Government of the Netherlands

microbiology↗

Bivalent COVID-19 vaccines boost the capacity of pre-existing SARS-CoV-2-specific memory B cells to cross-recognize Omicron subvariants

Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. We characterized the memory B-cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, and compared the immunogenicity with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one-month after a monovalent, BA.1 or BA.5 bivalent fourth dose COVID-19 vaccine. RBD-specific Bmem were quantified with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. All recipients had slightly increased WH1 RBD-specific Bmem numbers. Recognition of Omicron subvariants was not enhanced following monovalent vaccination, while both bivalent vaccines significantly increased WH1 RBD-specific Bmem cross-recognition of all Omicron subvariants tested by flow cytometry. Thus, Omicron-based bivalent vaccines can improve recognition of descendent Omicron subvariants by pre-existing, WH1-specific Bmem, beyond that of a conventional, monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants.

immunology↗

Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic

Zoonotic spillovers of viruses have occurred through the animal trade worldwide. The start of the COVID-19 pandemic was traced epidemiologically to the Huanan Wholesale Seafood Market, the site with the most reported wildlife vendors in the city of Wuhan, China. Here, we analyze publicly available qPCR and sequencing data from environmental samples collected in the Huanan market in early 2020. We demonstrate that the SARS-CoV-2 genetic diversity linked to this market is consistent with market emergence, and find increased SARS-CoV-2 positivity near and within a particular wildlife stall. We identify wildlife DNA in all SARS-CoV-2 positive samples from this stall. This includes species such as civets, bamboo rats, porcupines, hedgehogs, and one species, raccoon dogs, known to be capable of SARS-CoV-2 transmission. We also detect other animal viruses that infect raccoon dogs, civets, and bamboo rats. Combining metagenomic and phylogenetic approaches, we recover genotypes of market animals and compare them to those from other markets. This analysis provides the genetic basis for a short list of potential intermediate hosts of SARS-CoV-2 to prioritize for retrospective serological testing and viral sampling.

genomics↗

Differences in neuroinflammation in the olfactory bulb between D614G, Delta and Omicron BA.1 SARS-CoV-2 variants in the hamster model

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with various neurological complications. SARS-CoV-2 infection induces neuroinflammation in the central nervous system (CNS), whereat the olfactory bulb seems to be involved most frequently. Here we show differences in the neuroinvasiveness and neurovirulence among SARS-CoV-2 variants in the hamster model five days post inoculation. Replication in the olfactory mucosa was observed in all hamsters, but most prominent in D614 inoculated hamsters. We observed neuroinvasion into the CNS via the olfactory nerve in D614G-, but not Delta (B.1.617.2)- or Omicron BA.1 (B.1.1.529) inoculated hamsters. Neuroinvasion was associated with neuroinflammation in the olfactory bulb of hamsters inoculated with D614G but hardly in Delta or Omicron BA.1. Altogether, this indicates that there are differences in the neuroinvasive and neurovirulent potential among SARS-CoV-2 variants in the acute phase of the infection in the hamster model.

microbiology↗

Street RABV induces the cholinergic anti-inflammatory pathway in human monocyte-derived macrophages by binding to nAChr-a7, and upregulates the M2-c marker CD163

Rabies virus (RABV) is able to reach the central nervous system (CNS) without triggering a strong immune response, using multiple mechanisms to evade and suppress the host immune system. After infection via a bite or scratch from a rabid animal, RABV comes into contact with macrophages, which are the first antigen-presenting cells (APCs) that are recruited to the area and play an essential role in the onset of a specific immune response. It is poorly understood how RABV affects macrophages, and if the interaction contributes to the observed immune suppression. This study was undertaken to characterize the interactions between RABV and human monocyte-derived macrophages (MDMs). We showed that street RABV does not replicate in human MDMs. Using a recombinant trimeric RABV glycoprotein (RABV-tG) we showed binding to the nicotinic acetylcholine receptor alpha 7 (nAChr [a]7) on MDMs, and confirmed the specificity using the nAChr [a]7 antagonist alpha-bungarotoxin ([a]-BTX). We found that this binding induced the cholinergic anti-inflammatory pathway (CAP), characterized by a significant decrease in tumor necrosis factor [a] (TNF-[a]) upon LPS challenge. Using confocal microscopy we found that induction of the CAP is associated with significant cytoplasmic retention of nuclear factor {kappa}B (NF-{kappa}B). Co-cultures of human MDMs exposed to street RABV and autologous T cells further revealed that the observed suppression of MDMs affects their function as T cell activators as well, as we found a significant decrease in proliferation of CD8+ T cells. Lastly, using flow cytometric analysis we observed a significant increase in expression of CD163, hinting that street RABV is able to polarize macrophages towards a M2-c anti-inflammatory phenotype. Taken together, these results show that street RABV is capable of inducing an anti-inflammatory state in human macrophages, which affects T cell proliferation. Author summaryRabies virus (RABV) is transmitted by a bite or a scratch from an infected animal. Infection leads to a lethal encephalitis and once clinical symptoms occur, there is no effective treatment available. The virus is able to travel from the initial site of infection to the central nervous system without triggering a strong immune response, using multiple mechanisms to evade and suppress the immune system. Up to present it is unclear when and where this immunosuppression is initiated, and if local immune cells are involved as well. Understanding the complete mechanisms of immunosuppression by RABV is essential for the development and improvement of effective post-exposure treatments. In this paper we studied if RABV is able to suppress human primary macrophages as these will be the first antigen-presenting cells that are recruited to the site of infection, and are known to be important in initiating an efficient immune response. We show that RABV is able to bind, but not infect, human macrophages. Binding induces an anti-inflammatory pathway, which leads to limited T cell proliferation and directs macrophages towards and anti-inflammatory state. These results show that RABV-macrophage interactions might indeed be one of the early steps in the onset of RABV-induced immunosuppression.

immunology↗

SARS-CoV-2 is transmitted via contact and via the air between ferrets.

SARS-CoV-2, a coronavirus that newly emerged in China in late 2019 1,2 and spread rapidly worldwide, caused the first witnessed pandemic sparked by a coronavirus. As the pandemic progresses, information about the modes of transmission of SARS-CoV-2 among humans is critical to apply appropriate infection control measures and to slow its spread. Here we show that SARS-CoV-2 is transmitted efficiently via direct contact and via the air (via respiratory droplets and/or aerosols) between ferrets. Intranasal inoculation of donor ferrets resulted in a productive upper respiratory tract infection and long-term shedding, up to 11 to 19 days post-inoculation. SARS-CoV-2 transmitted to four out of four direct contact ferrets between 1 and 3 days after exposure and via the air to three out of four independent indirect recipient ferrets between 3 and 7 days after exposure. The pattern of virus shedding in the direct contact and indirect recipient ferrets was similar to that of the inoculated ferrets and infectious virus was isolated from all positive animals, showing that ferrets were productively infected via either route. This study provides experimental evidence of robust transmission of SARS-CoV-2 via the air, supporting the implementation of community-level social distancing measures currently applied in many countries in the world and informing decisions on infection control measures in healthcare settings 3.

microbiology↗