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Lia van der Hoek

Publications and source records attributed to Lia van der Hoek.

At least 19 recordsLinked to original sources
PubMed2026

Transmission of Anellovirus From Kidney-Donor to Pediatric Recipient: An Exploratory Study.

BACKGROUND: Among the most abundant viruses in the human blood virome are anelloviruses, including alpha-, beta-, and gammatorqueviruses (TTV, TTMV, and TTMDV). Whether anelloviruses are transmitted through kidney transplantation at a young age and subsequently persist in their new host is unknown. This study investigates the dynamics and composition of the anellome in the blood of six pediatric donor-recipient pairs, with monitoring beginning before transplantation and continuing until 2&#x2009;years after transplantation. METHODS: Donors were sampled once, before donation, while recipients were sampled before and multiple times after transplantation (median 6.5 samples). Quantitative PCR, rolling circle amplification, Illumina sequencing, and SCANellome V2 analysis were used to detect, characterize, and compare anellovirus presence in donors and recipients. RESULTS: At baseline, four out of six donors tested positive for TTV by quantitative anellovirus PCR, three of whom had sufficient viral loads to enable genomic comparison with their recipients. All recipients tested positive at baseline, five had a moderate viral load (<&#x2009;105 copies/mL), and one had >&#x2009;109 copies of TTV DNA/mL. This recipient was already immunosuppressed before transplantation, and only in this recipient was a donor-derived anellovirus identified. This lineage was detected among 15 other lineages in the recipient and matched one of the four lineages identified in the donor. CONCLUSION: This finding demonstrates that anellovirus transmission from donor to recipient occurs in pediatric kidney transplantation. This may be associated with pre-existing immunosuppression.

Humans↗
PubMed2006

Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes.

BACKGROUND: The genome of coronaviruses contains structural and non-structural genes, including several so-called accessory genes. All group 1b coronaviruses encode a single accessory protein between the spike and envelope genes, except for human coronavirus (HCoV) 229E. The prototype virus has a split gene, encoding the putative ORF4a and ORF4b proteins. To determine whether primary HCoV-229E isolates exhibit this unusual genome organization, we analyzed the ORF4a/b region of five current clinical isolates from The Netherlands and three early isolates collected at the Common Cold Unit (CCU) in Salisbury, UK. RESULTS: All Dutch isolates were identical in the ORF4a/b region at amino acid level. All CCU isolates are only 98% identical to the Dutch isolates at the nucleotide level, but more closely related to the prototype HCoV-229E (>98%). Remarkably, our analyses revealed that the laboratory adapted, prototype HCoV-229E has a 2-nucleotide deletion in the ORF4a/b region, whereas all clinical isolates carry a single ORF, 660 nt in size, encoding a single protein of 219 amino acids, which is a homologue of the ORF3 proteins encoded by HCoV-NL63 and PEDV. CONCLUSION: Thus, the genome organization of the group 1b coronaviruses HCoV-NL63, PEDV and HCoV-229E is identical. It is possible that extensive culturing of the HCoV-229E laboratory strain resulted in truncation of ORF4. This may indicate that the protein is not essential in cell culture, but the highly conserved amino acid sequence of the ORF4 protein among clinical isolates suggests that the protein plays an important role in vivo.

Aged↗
PubMed2006

Core structure of S2 from the human coronavirus NL63 spike glycoprotein.

Human coronavirus NL63 (HCoV-NL63) has recently been identified as a causative agent of acute respiratory tract illnesses in infants and young children. The HCoV-NL63 spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This viral entry process is a primary target for vaccine and drug development. HCoV-NL63 S is expressed as a single-chain glycoprotein and consists of an N-terminal receptor-binding domain (S1) and a C-terminal transmembrane fusion domain (S2). The latter contains two highly conserved heptad-repeat (HR) sequences that are each extended by 14 amino acids relative to those of the SARS coronavirus or the prototypic murine coronavirus, mouse hepatitis virus. Limited proteolysis studies of the HCoV-NL63 S2 fusion core identify an alpha-helical domain composed of a trimer of the HR segments N57 and C42. The crystal structure of this complex reveals three C42 helices entwined in an oblique and antiparallel manner around a central triple-stranded coiled coil formed by three N57 helices. The overall geometry comprises distinctive high-affinity conformations of interacting cross-sectional layers of the six helices. As a result, this structure is unusually stable, with an apparent melting temperature of 78 degrees C in the presence of the denaturant guanidine hydrochloride at 5 M concentration. The extended HR regions may therefore be required to prime the group 1 S glycoproteins for their fusion-activating conformational changes during viral entry. Our results provide an initial basis for understanding an intriguing interplay between the presence or absence of proteolytic maturation among the coronavirus groups and the membrane fusion activity of their S glycoproteins. This study also suggests a potential strategy for the development of improved HCoV-NL63 fusion inhibitors.

Amino Acid Sequence↗
PubMed2006

Mosaic structure of human coronavirus NL63, one thousand years of evolution.

Before the SARS outbreak only two human coronaviruses (HCoV) were known: HCoV-OC43 and HCoV-229E. With the discovery of SARS-CoV in 2003, a third family member was identified. Soon thereafter, we described the fourth human coronavirus (HCoV-NL63), a virus that has spread worldwide and is associated with croup in children. We report here the complete genome sequence of two HCoV-NL63 clinical isolates, designated Amsterdam 57 and Amsterdam 496. The genomes are 27,538 and 27,550 nucleotides long, respectively, and share the same genome organization. We identified two variable regions, one within the 1a and one within the S gene, whereas the 1b and N genes were most conserved. Phylogenetic analysis revealed that HCoV-NL63 genomes have a mosaic structure with multiple recombination sites. Additionally, employing three different algorithms, we assessed the evolutionary rate for the S gene of group Ib coronaviruses to be approximately 3 x 10(-4) substitutions per site per year. Using this evolutionary rate we determined that HCoV-NL63 diverged in the 11th century from its closest relative HCoV-229E.

Algorithms↗
PubMed2006

Identification of cell lines permissive for human coronavirus NL63.

Six cell lines routinely used in laboratories were tested for permissiveness to the infection with the newly identified human coronavirus NL63. Two monkey epithelial cell lines, LLC-MK2 and Vero-B4, showed a cytopathic effect (CPE) and clear viral replication, whereas no CPE or replication was observed in human lung fibroblasts MRC-5s. In Rhabdomyosarcoma cells, Madin-Darby-Canine-kidney cells and in an undefined monkey kidney cell line some replication was observed but massive exponential rise in virus yield lacked The results will lead to an improved routine diagnostic algorithm for the detection of the human coronavirus NL63.

Animals↗
PubMed2006

Identification of alternative amino acid substitutions in drug-resistant variants of the HIV-1 reverse transcriptase.

OBJECTIVE/DESIGN: To identify new drug-resistance-associated mutations in the HIV-1 reverse transcriptase (RT) protein, we screened the RT sequence database of our hospital for alternative amino acid substitutions at known RT drug-resistance positions. METHOD: The genotypic database used for this analysis contained 1322 RT sequences from 1015 patients. We analysed this RT database with a focus on alternative mutations at RT positions known to be involved in drug resistance. The patterns of drug resistance associated with these alternative mutations were investigated in a separate database containing genotype and drug-susceptibility results. RESULTS: We identified multiple alternative resistance-associated mutations at amino acid positions 44, 62, 67, 69, 70, 74, 75, 103, 181, 190, 210, and 219 in RT. Phenotypic analysis indicated that drug-resistance properties of the alternative Y181V and L74I mutants are similar, but not identical, to that of the well-known Y181C and L74V mutations. CONCLUSION: This initial survey indicates that many resistance-associated phenomena can be distilled from existing data. These findings endorse a more extensive analysis by computerized methods.

Anti-HIV Agents↗
PubMed2006

Human coronavirus NL63, a new respiratory virus.

From the mid-1960s onwards, it was believed that only two human coronavirus species infect humans: HCoV-229E and HCoV-OC43. Then, in 2003, a novel member of the coronavirus family was introduced into the human population: SARS-CoV, causing an aggressive lung disease. Fortunately, this virus was soon expelled from the human population, but it quickly became clear that the human coronavirus group contains more members then previously assumed, with HCoV-NL63 identified in 2004. Despite its recent discovery, ample results from HCoV-NL63 research have been described. We present an overview of the publications on this novel coronavirus.

Coronavirus↗
PubMed2006

Inhibition of human coronavirus NL63 infection at early stages of the replication cycle.

Human coronavirus NL63 (HCoV-NL63), a recently discovered member of the Coronaviridae family, has spread worldwide and is associated with acute respiratory illness in young children and elderly and immunocompromised persons. Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because the virus uses the same cellular receptor as severe acute respiratory syndrome-associated coronavirus. As there is currently no HCoV-NL63-specific and effective vaccine or drug therapy available, we evaluated several existing antiviral drugs and new synthetic compounds as inhibitors of HCoV-NL63, targeting multiple stages of the replication cycle. Of the 28 compounds that we tested, 6 potently inhibited HCoV-NL63 at early steps of the replication cycle. Intravenous immunoglobulins, heptad repeat 2 peptide, small interfering RNA1 (siRNA1), siRNA2, beta-D-N(4)-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 microg/ml, 2 microM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 microM, >200 nM, >200 nM, >100 microM, and 80 microM, respectively). These agents may be investigated further for the treatment of coronavirus infections.

Animals↗
PubMed2006

Evolution of transmitted HIV-1 with drug-resistance mutations in the absence of therapy: effects on CD4+ T-cell count and HIV-1 RNA load.

Sequence analysis of HIV-1 from 440 therapy-naive individuals included within the CASCADE study, who seroconverted within 18 months of the last negative test, identified 65 persons infected with a strain carrying resistance-associated mutations. Population-based sequencing was performed for 20 of these individuals during the therapy-free follow-up period. The median time of follow-up was 15 months (interquartile range from 10 to 23 months). Of these individuals, 12 showed subsequent evolution at the resistance positions, whereas the virus of 8 people was stable during this period. In the reverse transcriptase (RT) gene, the drug-resistant 215Y or 215F codons evolved to alternative codons in all six cases, 70R reverted to the wild-type 70K in 3 of the 4 individuals, 67N evolved only in 1 of 4 patients to a wild-type 67D, 215S evolved to wild-type 215T in 1 of 3 patients, 219N evolved to 219K in 1 of 2 patients, and one patient with 184V reversed to the wild-type 184M. The 181C variant evolved to the wild-type 181Y in 1 of 2 individuals. These codon changes were caused by single nucleotide mutations. No evolution was observed for other RT mutations: 41L, 69D, 69N, 190S, 210W, 215L, 215C, 215E and 219Q. In the protease gene, resistance mutations 84V and 90M were stable in 2 individuals. Comparing the CD4+ T-cell count of the 12 evolving versus the 8 stable cases revealed no statistically significant difference at the date of the first sequence following seroconversion. Interestingly, a lower CD4+ T-cell count was observed in the group without evolution at the second sequence time point (P = 0.043). No difference in HIV-1 RNA load was observed. These results, together with the apparent pressure to mutate at the resistance-associated positions exemplify the decreased fitness of viruses carrying 21 5Y/F, 70R or 184V.

Anti-HIV Agents↗
PubMed2005

Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms: data from seroconverters in the CASCADE collaboration from 1987 to 2003.

OBJECTIVES: To examine factors influencing the rate of transmitted drug resistance (TDR) among seroconverters, with particular emphasis on 3 widely used genotypic drug resistance algorithms. METHODS: The study used data from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration of seroconverter cohorts in Europe and Canada. Genotypic resistance data were derived within 18 months of the last seronegative test or date of laboratory evidence of acute infection and before the initiation of antiretroviral therapy. The Stanford algorithm was used to analyze each individual's nucleotide sequence. A multivariate logistic model was used to assess independent relationships between the presence of TDR and exposure category, sex, age at seroconversion, and year of seroconversion. The paper also describes 3 alternative definitions of resistance: the Stanford algorithm, the key resistance mutations defined by the International AIDS Society, and the Agence Nationale de Recherches sur le Sida (ANRS) algorithm. RESULTS: Forty-five of 438 patients (10.3%) seroconverting between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty patients (9.1%) showed resistance mutations to only 1 class of antiretroviral drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral therapy. It was suggested that individuals seroconverting later in calendar time were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003, respectively, compared with pre-1996; P trend = 0.08). This trend was apparent regardless of the definition of TDR used. The total estimated proportion of individuals with TDR varied between 10.3% and 15.5% according to which definition was used. CONCLUSIONS: Evidence was found for the rise of TDR over time. A specific definition of what constitutes TDR rather than a simple list of mutations is needed.

Adolescent↗
PubMed2005

Human coronavirus NL63 is not detected in the respiratory tracts of children with acute Kawasaki disease.

Kawasaki disease (KD) is a self-limited, systemic vasculitis of children for which an infectious trigger is suspected. Recently, an association between KD and human coronavirus (HCoV)-New Haven (NH) was reported, on the basis of polymerase chain reaction (PCR) with primers that also amplified HCoV-NL63. We investigated the possible association between these HCoVs in the respiratory tract and KD by reverse-transcriptase (RT) PCR and viral culture in a geographically and ethnically diverse population. Only 1 (2%) of 48 patients with acute KD was positive by RT-PCR for HCoV-NL63/NH in a nasopharyngeal swab. These data do not support an association between these HCoVs and KD.

Child↗
PubMed2005

Croup is associated with the novel coronavirus NL63.

BACKGROUND: The clinical relevance of infections with the novel human coronavirus NL63 (HCoV-NL63) has not been investigated systematically. We therefore determined its association with disease in young children with lower respiratory tract infection (LRTI). METHODS AND FINDINGS: Nine hundred forty-nine samples of nasopharyngeal secretions from children under 3 y of age with LRTIs were analysed by a quantitative HCoV-NL63-specific real-time PCR. The samples had been collected from hospitalised patients and outpatients from December 1999 to October 2001 in four different regions in Germany as part of the prospective population-based PRI.DE study and analysed for RNA from respiratory viruses. Forty-nine samples (5.2%), mainly derived from the winter season, were positive for HCoV-NL63 RNA. The viral RNA was more prevalent in samples from outpatients (7.9%) than from hospitalised patients (3.2%, p = 0.003), and co-infection with either respiratory syncytial virus or parainfluenza virus 3 was observed frequently. Samples in which only HCoV-NL63 RNA could be detected had a significantly higher viral load than samples containing additional respiratory viruses (median 2.1 x 10(6) versus 2.7 x 10(2) copies/ml, p = 0.0006). A strong association with croup was apparent: 43% of the HCoV-NL63-positive patients with high HCoV-NL63 load and absence of co-infection suffered from croup, compared to 6% in the HCoV-NL63-negative group, p < 0.0001. A significantly higher fraction (17.4%) of samples from croup patients than from non-croup patients (4.2%) contained HCoV-NL63 RNA. CONCLUSION: HCoV-NL63 infections occur frequently in young children with LRTI and show a strong association with croup, suggesting a causal relationship.

Child, Preschool↗