Leo Heyndrickx - Academia.edu (original) (raw)

Papers by Leo Heyndrickx

Research paper thumbnail of P04-52 LB. The importance of well-defined HIV-1 neutralization assays

Retrovirology, Oct 1, 2009

Research paper thumbnail of A novel high-throughput cellular screening assay for the discovery of HIV-1 integrase inhibitors

Journal of Virological Methods, Feb 1, 2012

The discovery of HIV-1 integrase inhibitors has been enabled by high-throughput screening and rat... more The discovery of HIV-1 integrase inhibitors has been enabled by high-throughput screening and rational design of novel chemotypes. Traditionally, biochemical assays focusing on the strand transfer activity of integrase have been used to screen compound libraries for identification of novel inhibitors. In contrast, cellular screening assays enable a phenotypic or multi-target approach, and may result in identification of compounds inhibiting integrase in its natural context, the pre-integration complex. Furthermore, a cellular assay encompassing 3' processing, strand transfer and nuclear import may lead to the identification of compounds with novel mechanisms of action targeting cellular and viral factors. Therefore, a cellular screening assay was developed, which focused on integrase activity, where infection of MT4 cells with an HIV-1 based lentiviral vector was synchronized by temporary arrest at the reverse transcriptase step and subsequent release to enable integration. The assay was validated using a panel of antivirals and proved to be a robust cellular screening assay for the identification of novel integrase inhibitors.

Research paper thumbnail of Replicative fitness of CCR5-using and CXCR4-using human immunodeficiency virus type 1 biological clones

Research paper thumbnail of Predominance of infection with HIV-1 circulating recombinant form CRF02_AG in major Cameroonian cities and towns

AIDS, 2002

... Constance Williamsa. ... New Microbiologica Human immunodeficiency virus type 1 intersubtype ... more ... Constance Williamsa. ... New Microbiologica Human immunodeficiency virus type 1 intersubtype recombinants predominate in the AIDS epidemic in Cameroon Torimiro, JN; D'Arrigo, R; Takou, D; Nanfack, A; Pizzi, D; Ngong, I; Carr, JK; Joseph, FP; Perno, CF; Cappelli, G New ...

Research paper thumbnail of Macrophage-tropism of HIV-1 isolates of difference genetic subtypes

Research paper thumbnail of Isolation of HIV-1 RNA from plasma: evaluation of seven different methods for extraction (part two)

Journal of Virological Methods, Dec 1, 1998

Some new commercial methods for the extraction of viral RNA have been introduced recently. In add... more Some new commercial methods for the extraction of viral RNA have been introduced recently. In addition to the study published previously (Verhofstede, C., Reniers, S., Van Wanzeele. F., Plum J., 1996. AIDS 8, 1421-1427), seven different methods (four newly developed and three reference methods) for extraction of HIV-1 RNA from plasma have been evaluated. The RNA preparation method that gave the best results (acceptable reproducibility, highest sensitivity, reasonable price, fast and easy to perform), was the QIAamp Viral RNA kit from QIAgen. The High Pure Viral RNA Kit (Boehringer Mannheim) as well as the non-commercialised extraction kits were also very sensitive. The non-commercial tests seem less suitable for routine use and for the processing of large number of samples. Two methods, RNA Insta-Pure LS (Eurogentec) and PANext RNA extraction kit 1 (NTL, PANsystems GmbH) are not adapted for HIV plasma extraction. The single step methods using glass fibre or silica column are rapid (from 60 to 75 min depending on the number of wash steps) and although the price is high they are cheaper than the Boom extraction methods: High Pure Viral RNA Kit (Boehringer Mannheim) ($3.3/sample), QIAamp Viral RNA Kit (Qiagen) ($3.6/sample), Boom extraction ($5/sample). The Qiagen kit is the only kit that combines sensitivity with reproducibility, it is commercialised, rapid and affordable in price and can be automated. For most of the methods evaluated the inter-test variability was acceptable (mean variation coefficient between duplicate extractions varied between 26.4 and 48.6%).

Research paper thumbnail of Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies

Research paper thumbnail of Development of a One-Tube Multiplex Reverse Transcriptase-Polymerase Chain Reaction Assay for the Simultaneous Amplification of HIV Type 1 Group MgagandenvHeteroduplex Mobility Assay Fragments

AIDS Research and Human Retroviruses, Oct 10, 2000

Research paper thumbnail of Third dose of COVID-19 mRNA vaccine closes the gap in immune response between naïve nursing home residents and healthy adults

Research paper thumbnail of Antibody response against SARS-CoV-2 Delta and Omicron variants after third-dose BNT162b2 vaccination in allo-HCT recipients

Research paper thumbnail of Confirmation and differentiation of antibodies to human immunodeficiency virus 1 and 2 with a strip-based assay including recombinant antigens and synthetic peptides

Clinical Chemistry, 1991

We evaluated the use of the INNO-LIA HIV-1/HIV-2 Ab test (LIA HIV; Innogenetics) for the confirma... more We evaluated the use of the INNO-LIA HIV-1/HIV-2 Ab test (LIA HIV; Innogenetics) for the confirmation of antibodies to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). The test includes three recombinant HIV-1 proteins: p24 (gag), p17 (gag), and endonuclease (p31; pol), in combination with two synthetic peptides derived from the env gene of HIV-1 and one synthetic peptide selected from the env gene of HIV-2. Analysis of 450 sera from blood donors, 220 sera from patients with non-HIV pathology, and 28 Western blot (WB) p24-only reactive sera revealed no false-positive results, and the rate of indeterminate results was substantially lower than that with WB. Testing of 334 WB-confirmed HIV antibody-positive sera (309 HIV-1; 25 HIV-2) revealed no false-negative results. In two of seven seroconversion panels tested, LIA HIV detected the presence of HIV antibodies before WB did. In the other five panels, LIA HIV and WB confirmed the presence of HIV antibodies in the same sa...

Research paper thumbnail of Superimposing incident sexually transmitted infections on HIV phylogram to investigate possible misclassification of men who have sex with men as heterosexuals in a cohort in Antwerp, Belgium

International Journal of STD & AIDS, 2019

In this study, we assessed if the superimposition of incident sexually transmitted infections (ST... more In this study, we assessed if the superimposition of incident sexually transmitted infections (STIs) on HIV phylogenetic analyses could reveal possible sexual behaviour misclassifications in our HIV-infected population. HIV-1 sequences collected between 1997 and 2014 from 1169 individuals attending a HIV clinic in Antwerp, Belgium were analysed to infer a partial HIV transmission network. Individual demographic, clinical and laboratory data collected during routine HIV follow-up were used to compare clustered and non-clustered individuals using logistic regression analyses. In total, 438 (37.5%) individuals were identified in 136 clusters, including 76 transmission pairs and 60 clusters consisting of three or more individuals. Individuals in a cluster were more likely to have a history of syphilis, Chlamydia and/or gonorrhoea (P < 0.05); however, when analyses were stratified by HIV transmission risk groups (heterosexual and men who have sex with men [MSM]), this association only...

Research paper thumbnail of In-vitro viral suppressive capacity correlates with immune checkpoint marker expression on peripheral CD8+ T cells in treated HIV-positive patients

Research paper thumbnail of Genetic and Phylogenetic Analysis of env Subtypes G and H in Central Africa

AIDS Research and Human Retroviruses, 1994

... Genetic and Phylogenetic Analysis of env Subtypes G and H in Central Africa ... Distance calc... more ... Genetic and Phylogenetic Analysis of env Subtypes G and H in Central Africa ... Distance calculation, tree construction, and bootstrap analysis were realized with the software package TREECON.6 A phylogenetic tree based on the common 900-bp env fragments was generated. ...

Research paper thumbnail of HIV-1 group O and group M dual infection in B�nin

Research paper thumbnail of Characterisation of Transmitted and Non-transmitted HIV in Index-recipient Transmission Pairs

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Newly Developed gp140 Trimeric Formulations Induce Inter-subtype HIV-1 Neutralization When Administered After DNA Prime Regimen to Cynomolgus Macaques

Research paper thumbnail of Resistance Profile of the Diaryltriazine Non-nucleoside Reverse Transcriptase Inhibitor and Candidate Microbicide UAMC01398

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Diagnosis of HIV-1 group O infection by polymerase chain reaction

Research paper thumbnail of Design and evaluation of an in-house HIV-1 (group M and O), SIVmnd and SIVcpz antigen capture assay

Journal of Virological Methods, 1998

... To design an in-house antigen capture ... positive sample signals were obtained when using pu... more ... To design an in-house antigen capture ... positive sample signals were obtained when using purified IgG 1 for coating at a concentration of 4 μg/well and purified and conjugated IgG 2 for detection at a concentration of 5 μg ml −1 . The anti-p24 titer for IgG 1 was 1/10 000 and 1 ...

Research paper thumbnail of P04-52 LB. The importance of well-defined HIV-1 neutralization assays

Retrovirology, Oct 1, 2009

Research paper thumbnail of A novel high-throughput cellular screening assay for the discovery of HIV-1 integrase inhibitors

Journal of Virological Methods, Feb 1, 2012

The discovery of HIV-1 integrase inhibitors has been enabled by high-throughput screening and rat... more The discovery of HIV-1 integrase inhibitors has been enabled by high-throughput screening and rational design of novel chemotypes. Traditionally, biochemical assays focusing on the strand transfer activity of integrase have been used to screen compound libraries for identification of novel inhibitors. In contrast, cellular screening assays enable a phenotypic or multi-target approach, and may result in identification of compounds inhibiting integrase in its natural context, the pre-integration complex. Furthermore, a cellular assay encompassing 3&amp;amp;amp;amp;#39; processing, strand transfer and nuclear import may lead to the identification of compounds with novel mechanisms of action targeting cellular and viral factors. Therefore, a cellular screening assay was developed, which focused on integrase activity, where infection of MT4 cells with an HIV-1 based lentiviral vector was synchronized by temporary arrest at the reverse transcriptase step and subsequent release to enable integration. The assay was validated using a panel of antivirals and proved to be a robust cellular screening assay for the identification of novel integrase inhibitors.

Research paper thumbnail of Replicative fitness of CCR5-using and CXCR4-using human immunodeficiency virus type 1 biological clones

Research paper thumbnail of Predominance of infection with HIV-1 circulating recombinant form CRF02_AG in major Cameroonian cities and towns

AIDS, 2002

... Constance Williamsa. ... New Microbiologica Human immunodeficiency virus type 1 intersubtype ... more ... Constance Williamsa. ... New Microbiologica Human immunodeficiency virus type 1 intersubtype recombinants predominate in the AIDS epidemic in Cameroon Torimiro, JN; D'Arrigo, R; Takou, D; Nanfack, A; Pizzi, D; Ngong, I; Carr, JK; Joseph, FP; Perno, CF; Cappelli, G New ...

Research paper thumbnail of Macrophage-tropism of HIV-1 isolates of difference genetic subtypes

Research paper thumbnail of Isolation of HIV-1 RNA from plasma: evaluation of seven different methods for extraction (part two)

Journal of Virological Methods, Dec 1, 1998

Some new commercial methods for the extraction of viral RNA have been introduced recently. In add... more Some new commercial methods for the extraction of viral RNA have been introduced recently. In addition to the study published previously (Verhofstede, C., Reniers, S., Van Wanzeele. F., Plum J., 1996. AIDS 8, 1421-1427), seven different methods (four newly developed and three reference methods) for extraction of HIV-1 RNA from plasma have been evaluated. The RNA preparation method that gave the best results (acceptable reproducibility, highest sensitivity, reasonable price, fast and easy to perform), was the QIAamp Viral RNA kit from QIAgen. The High Pure Viral RNA Kit (Boehringer Mannheim) as well as the non-commercialised extraction kits were also very sensitive. The non-commercial tests seem less suitable for routine use and for the processing of large number of samples. Two methods, RNA Insta-Pure LS (Eurogentec) and PANext RNA extraction kit 1 (NTL, PANsystems GmbH) are not adapted for HIV plasma extraction. The single step methods using glass fibre or silica column are rapid (from 60 to 75 min depending on the number of wash steps) and although the price is high they are cheaper than the Boom extraction methods: High Pure Viral RNA Kit (Boehringer Mannheim) ($3.3/sample), QIAamp Viral RNA Kit (Qiagen) ($3.6/sample), Boom extraction ($5/sample). The Qiagen kit is the only kit that combines sensitivity with reproducibility, it is commercialised, rapid and affordable in price and can be automated. For most of the methods evaluated the inter-test variability was acceptable (mean variation coefficient between duplicate extractions varied between 26.4 and 48.6%).

Research paper thumbnail of Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies

Research paper thumbnail of Development of a One-Tube Multiplex Reverse Transcriptase-Polymerase Chain Reaction Assay for the Simultaneous Amplification of HIV Type 1 Group MgagandenvHeteroduplex Mobility Assay Fragments

AIDS Research and Human Retroviruses, Oct 10, 2000

Research paper thumbnail of Third dose of COVID-19 mRNA vaccine closes the gap in immune response between naïve nursing home residents and healthy adults

Research paper thumbnail of Antibody response against SARS-CoV-2 Delta and Omicron variants after third-dose BNT162b2 vaccination in allo-HCT recipients

Research paper thumbnail of Confirmation and differentiation of antibodies to human immunodeficiency virus 1 and 2 with a strip-based assay including recombinant antigens and synthetic peptides

Clinical Chemistry, 1991

We evaluated the use of the INNO-LIA HIV-1/HIV-2 Ab test (LIA HIV; Innogenetics) for the confirma... more We evaluated the use of the INNO-LIA HIV-1/HIV-2 Ab test (LIA HIV; Innogenetics) for the confirmation of antibodies to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). The test includes three recombinant HIV-1 proteins: p24 (gag), p17 (gag), and endonuclease (p31; pol), in combination with two synthetic peptides derived from the env gene of HIV-1 and one synthetic peptide selected from the env gene of HIV-2. Analysis of 450 sera from blood donors, 220 sera from patients with non-HIV pathology, and 28 Western blot (WB) p24-only reactive sera revealed no false-positive results, and the rate of indeterminate results was substantially lower than that with WB. Testing of 334 WB-confirmed HIV antibody-positive sera (309 HIV-1; 25 HIV-2) revealed no false-negative results. In two of seven seroconversion panels tested, LIA HIV detected the presence of HIV antibodies before WB did. In the other five panels, LIA HIV and WB confirmed the presence of HIV antibodies in the same sa...

Research paper thumbnail of Superimposing incident sexually transmitted infections on HIV phylogram to investigate possible misclassification of men who have sex with men as heterosexuals in a cohort in Antwerp, Belgium

International Journal of STD & AIDS, 2019

In this study, we assessed if the superimposition of incident sexually transmitted infections (ST... more In this study, we assessed if the superimposition of incident sexually transmitted infections (STIs) on HIV phylogenetic analyses could reveal possible sexual behaviour misclassifications in our HIV-infected population. HIV-1 sequences collected between 1997 and 2014 from 1169 individuals attending a HIV clinic in Antwerp, Belgium were analysed to infer a partial HIV transmission network. Individual demographic, clinical and laboratory data collected during routine HIV follow-up were used to compare clustered and non-clustered individuals using logistic regression analyses. In total, 438 (37.5%) individuals were identified in 136 clusters, including 76 transmission pairs and 60 clusters consisting of three or more individuals. Individuals in a cluster were more likely to have a history of syphilis, Chlamydia and/or gonorrhoea (P < 0.05); however, when analyses were stratified by HIV transmission risk groups (heterosexual and men who have sex with men [MSM]), this association only...

Research paper thumbnail of In-vitro viral suppressive capacity correlates with immune checkpoint marker expression on peripheral CD8+ T cells in treated HIV-positive patients

Research paper thumbnail of Genetic and Phylogenetic Analysis of env Subtypes G and H in Central Africa

AIDS Research and Human Retroviruses, 1994

... Genetic and Phylogenetic Analysis of env Subtypes G and H in Central Africa ... Distance calc... more ... Genetic and Phylogenetic Analysis of env Subtypes G and H in Central Africa ... Distance calculation, tree construction, and bootstrap analysis were realized with the software package TREECON.6 A phylogenetic tree based on the common 900-bp env fragments was generated. ...

Research paper thumbnail of HIV-1 group O and group M dual infection in B�nin

Research paper thumbnail of Characterisation of Transmitted and Non-transmitted HIV in Index-recipient Transmission Pairs

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Newly Developed gp140 Trimeric Formulations Induce Inter-subtype HIV-1 Neutralization When Administered After DNA Prime Regimen to Cynomolgus Macaques

Research paper thumbnail of Resistance Profile of the Diaryltriazine Non-nucleoside Reverse Transcriptase Inhibitor and Candidate Microbicide UAMC01398

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Diagnosis of HIV-1 group O infection by polymerase chain reaction

Research paper thumbnail of Design and evaluation of an in-house HIV-1 (group M and O), SIVmnd and SIVcpz antigen capture assay

Journal of Virological Methods, 1998

... To design an in-house antigen capture ... positive sample signals were obtained when using pu... more ... To design an in-house antigen capture ... positive sample signals were obtained when using purified IgG 1 for coating at a concentration of 4 μg/well and purified and conjugated IgG 2 for detection at a concentration of 5 μg ml −1 . The anti-p24 titer for IgG 1 was 1/10 000 and 1 ...