The emergence of the SARS-CoV-2 variant of concern Omicron (Pango lineage B.1.1.529), first ident... more The emergence of the SARS-CoV-2 variant of concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections1. Here we investigated Omicron escape from neutralization by antibodies from South African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination from individuals who were vaccinated and previously infected with SARS-CoV-2 or vaccinated with no evidence of previous infection. We isolated and sequence-confirmed live Omicron virus from an infected person and observed that Omicron requires the angiotensin-converting enzyme 2 (ACE2) receptor to infect cells. We compared plasma neutralization of Omicron relative to an ancestral SARS-CoV-2 strain and found that neutralization of ancestral virus was much higher in infected and vaccinated individuals compared with the vaccinated-only participants. However, both groups showed a 22-fold reduction in vaccine-elicited neutralization by the Omicron variant. Participants who were vaccinated and had previously been infected exhibited residual neutralization of Omicron similar to the level of neutralization of the ancestral virus observed in the vaccination-only group. These data support the notion that reasonable protection against Omicron may be maintained using vaccination approaches.
Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely... more Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV
Jaagsiekte, or ovine pulmonary adenomatosis, is caused by a recently discovered retrovirus. The v... more Jaagsiekte, or ovine pulmonary adenomatosis, is caused by a recently discovered retrovirus. The virus cannot be cultivated in vitro at present, but a procedure is described for the isolation and purification of small amounts in the form of immune complexes with IgA from affected lungs. The virion was shown to possess a 70S RNA genome which can be transcribed by an endogenous reverse transcriptase. Nine size from 94 000 to 25 000 daltons, were found in purified preparations. Using neutralization of the viral reverse transcriptase and an enzyme immunoassay as criteria, no serological relationship could be demonstrated to representatives of type B, C and C oncoviruses, or to bovine leukemia virus, maedi-visna virus of sheep or caprine arthritis-encephalitis virus.
The genome of the jaagsiekte (JS) retrovirus (JSRV), the etiological agent of sheep pulmonary ade... more The genome of the jaagsiekte (JS) retrovirus (JSRV), the etiological agent of sheep pulmonary adenomatosis (jaagsiekte), has been identified, isolated, and partly cloned. The JSRV genome is ca. 8.7 kb long. cDNA of the genomic RNA was synthesized and cloned. A clone, JS 46.1, was isolated and characterized. It has an insert of 2.1 kb which hybridizes to the same 8.7-kb RNA in all the JSRV-infected sheep lung washes tested but does not hybridize to maedi-visna virus, a sheep lentivirus often found coinfecting JSRV-infected lungs. Comparison of the amino acid sequence encoded by JS 46.1 with those encoded by other retroviruses revealed that JSRV has homology to the type D and B oncoviruses and to human endogenous retrovirus.
Current topics in microbiology and immunology, 2003
Jaagsiekte (JS), a contagious cancer affecting the lungs of sheep has been called many names over... more Jaagsiekte (JS), a contagious cancer affecting the lungs of sheep has been called many names over the years. At a recent workshop in Missilac, France it was agreed that the disease would be called ovine pulmonary adenocarcinoma (OPA). The disease is caused by an infectious retrovirus called jaagsiekte sheep retrovirus (JSRV). This chapter focuses on the early research that led up to the isolation, cloning and sequencing of the exogenous infectious form of JSRV and the demonstration that it has an endogenous counter part that is present in all sheep. As there was no in vitro production source of the virus much of the early research focused on the in vivo production and purification of the virus to obtain sufficient material to use to identify the viral proteins and purify the viral genetic material. Typically, new born lambs were inoculated intra-tracheally with concentrated lung lavage from previously infected sheep lungs. The optimal purification involved the concentration of lung ...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2001
The use of pyrazinamide (PZA) is important for the treatment of Mycobacterium tuberculosis as it ... more The use of pyrazinamide (PZA) is important for the treatment of Mycobacterium tuberculosis as it is bactericidal to semi-dormant mycobacteria that are not affected by other drugs. The incidence of resistance to PZA and other drugs used in the treatment of M. tuberculosis is increasing in South Africa. To characterise the pncA gene of M. tuberculosis isolates from Gauteng, South Africa, and to develop a rapid diagnostic method. The pncA gene and the putative regulatory gene were characterised by sequence analysis in a total of six PZA susceptible and 15 resistant isolates. The association with classical PZA susceptibility testing and PZase activity was determined. All PZA-resistant isolates were PZase negative as well as resistant to at least one other anti-tuberculosis drugs. Mutations were identified throughout the length of the pncA gene in 10/15 PZA-resistant isolates. Five lacked PZase activity, but the wild type pncA sequence was present. In all six PZase-positive strains, a PZ...
Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2000
Genotypic analysis of isoniazid (INH) resistance in 79 isolates of M. tuberculosis (MTB) was unde... more Genotypic analysis of isoniazid (INH) resistance in 79 isolates of M. tuberculosis (MTB) was undertaken by PCR-single strand conformation polymorphism (SSCP), Msp1 restriction enzyme analysis and sequence analysis of specific regions of three genes (part of the coding sequence of katG, and promoter regions of the inhA operon and ahpC) in order to determine the particular allelic variants within these genes. The epidemiologic relatedness was determined using IS6110 and polymorphic G-C region (PGRS (MTB484(1)) based restriction fragment length polymorphism (RFLP). Mutations in katG, inhA locus and ahpC were identified in 77/79, 19/79 and 10/79 isolates respectively. The ability of PCR-SSCP to detect mutations associated with INH resistance in katG, inhA and ahpC genes was 100% (CI 91.2-99.7%), 98.7% (CI 74.0-99.9%), and 100% (CI 69.2-100%) respectively. Specificity was 100%. All isolates with mutations in the 209 bp fragment of the MTB katG gene containing the Ser315Thr codon were pos...
Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung tumour of sheep ... more Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung tumour of sheep known as sheep pulmonary adenomatosis (syn: ovine pulmonary carcinoma, jaagsiekte). JSRV exhibits a simple genetic organization, characteristic of the type D and type B retroviruses, with the canonical retroviral sequences gag, pro, pol and env encoding the structural proteins of the virion. An additional open reading frame (orf-x), of approximately 500 bp overlapping pol, is present in the only two complete sequences of JSRV published to date. Since very little information is available on the biology of JSRV it is important to establish if orf-x is conserved between different virus isolates. In this study we analysed the orf-x region of JSRV isolates collected from the United Kingdom, Italy, Spain and South Africa. In addition we also analysed the presence of orf-x in JSRV-related endogenous sequences (enJSRVs) present in the sheep genome. Orf-x was highly conserved in all the exogenous...
The Veterinary clinics of North America. Food animal practice, 1997
As retrovirus-induced neoplasms of the respiratory epithelium of sheep and goats, OPC and ENT ran... more As retrovirus-induced neoplasms of the respiratory epithelium of sheep and goats, OPC and ENT rank as economically important diseases in many countries of the world. They are also important as models of retroviral carcinogenesis of the secretory epithelium of the respiratory system. Control of both diseases is dependent on development and application of sensitive and specific assays for identification of carrier animals infected with the causative agents of these diseases. Recent progress in characterization of type D/B retroviruses associated with the diseases and development of new reagents for the immunologic or molecular detection of antiviral antibodies, viral proteins, or viral nucleic acids bodes well for improved control or prevention of these diseases.
The Onderstepoort journal of veterinary research, 1986
In the course of attempts to grow the jaagsiekte retrovirus in cell culture, a typical lentivirus... more In the course of attempts to grow the jaagsiekte retrovirus in cell culture, a typical lentivirus was isolated for the first time in South Africa from adenomatous lungs. Morphologically the virus could not be distinguished from other lentiviruses, but serologically it was shown to be more closely related to visna virus than to caprine arthritis-encephalitis virus. However, a preliminary restriction enzyme analysis of the linear proviral DNA of this new lentivirus (SA-DMVV) revealed that it is significantly district from visna virus and CAEV and therefore may represent a third type of lentivirus. Antibodies to the virus were demonstrated in a number of sheep in various parts of the country, but a direct link to a disease condition was not found. Attempts to produce lung lesions by intratracheal injection of the virus have been unsuccessful to date but a transient arthritis was produced by intraarticular inoculation. Viral replication seems to be enhanced in jaagsiekte lungs.
The Onderstepoort journal of veterinary research, 1988
A South African isolate of ovine lentivirus was shown to cause a mild immunosuppression in sheep,... more A South African isolate of ovine lentivirus was shown to cause a mild immunosuppression in sheep, reflected by a reduced delayed hypersensitivity reaction. This effect, measured in terms of skin swelling after intradermal inoculation with tuberculin, showed a positive linear relationship with the latency period before the appearance of jaagsiekte symptoms in animals co-infected with JSRV, as well as with the activity of monocytes. In a parallel study, increased susceptibility of lentivirus-infected sheep to infection with Pasteurella haemolytica was demonstrated. It is concluded that the lentivirus may play an enhancing role in both viral and bacterial infections of sheep by compromising the host's cellular immune response.
The complete genome of the jaagsiekte sheep retrovirus (JSRV), the suspected etiological agent of... more The complete genome of the jaagsiekte sheep retrovirus (JSRV), the suspected etiological agent of ovine pulmonary carcinoma, has been cloned from viral particles secreted in lung exudates of affected animals and sequenced. The genome is 7,462 nucleotides long and exhibits a genetic organization characteristic of the type B and D oncoviruses. Comparison of the amino acid sequences of JSRV proteins with those of other retrovirus proteins and phylogenetic studies suggest that JSRV diverged from its type B and D lineage after the type B mouse mammary tumor virus but before the type D oncoviruses captured the env gene of a reticuloendotheliosislike virus. Southern blot studies show that closely related sequences are present in sheep and goat normal genomic DNA, indicating that JSRV could be endogenous in ovine and caprine species.
The emergence of the SARS-CoV-2 variant of concern Omicron (Pango lineage B.1.1.529), first ident... more The emergence of the SARS-CoV-2 variant of concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections1. Here we investigated Omicron escape from neutralization by antibodies from South African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination from individuals who were vaccinated and previously infected with SARS-CoV-2 or vaccinated with no evidence of previous infection. We isolated and sequence-confirmed live Omicron virus from an infected person and observed that Omicron requires the angiotensin-converting enzyme 2 (ACE2) receptor to infect cells. We compared plasma neutralization of Omicron relative to an ancestral SARS-CoV-2 strain and found that neutralization of ancestral virus was much higher in infected and vaccinated individuals compared with the vaccinated-only participants. However, both groups showed a 22-fold reduction in vaccine-elicited neutralization by the Omicron variant. Participants who were vaccinated and had previously been infected exhibited residual neutralization of Omicron similar to the level of neutralization of the ancestral virus observed in the vaccination-only group. These data support the notion that reasonable protection against Omicron may be maintained using vaccination approaches.
Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely... more Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV
Jaagsiekte, or ovine pulmonary adenomatosis, is caused by a recently discovered retrovirus. The v... more Jaagsiekte, or ovine pulmonary adenomatosis, is caused by a recently discovered retrovirus. The virus cannot be cultivated in vitro at present, but a procedure is described for the isolation and purification of small amounts in the form of immune complexes with IgA from affected lungs. The virion was shown to possess a 70S RNA genome which can be transcribed by an endogenous reverse transcriptase. Nine size from 94 000 to 25 000 daltons, were found in purified preparations. Using neutralization of the viral reverse transcriptase and an enzyme immunoassay as criteria, no serological relationship could be demonstrated to representatives of type B, C and C oncoviruses, or to bovine leukemia virus, maedi-visna virus of sheep or caprine arthritis-encephalitis virus.
The genome of the jaagsiekte (JS) retrovirus (JSRV), the etiological agent of sheep pulmonary ade... more The genome of the jaagsiekte (JS) retrovirus (JSRV), the etiological agent of sheep pulmonary adenomatosis (jaagsiekte), has been identified, isolated, and partly cloned. The JSRV genome is ca. 8.7 kb long. cDNA of the genomic RNA was synthesized and cloned. A clone, JS 46.1, was isolated and characterized. It has an insert of 2.1 kb which hybridizes to the same 8.7-kb RNA in all the JSRV-infected sheep lung washes tested but does not hybridize to maedi-visna virus, a sheep lentivirus often found coinfecting JSRV-infected lungs. Comparison of the amino acid sequence encoded by JS 46.1 with those encoded by other retroviruses revealed that JSRV has homology to the type D and B oncoviruses and to human endogenous retrovirus.
Current topics in microbiology and immunology, 2003
Jaagsiekte (JS), a contagious cancer affecting the lungs of sheep has been called many names over... more Jaagsiekte (JS), a contagious cancer affecting the lungs of sheep has been called many names over the years. At a recent workshop in Missilac, France it was agreed that the disease would be called ovine pulmonary adenocarcinoma (OPA). The disease is caused by an infectious retrovirus called jaagsiekte sheep retrovirus (JSRV). This chapter focuses on the early research that led up to the isolation, cloning and sequencing of the exogenous infectious form of JSRV and the demonstration that it has an endogenous counter part that is present in all sheep. As there was no in vitro production source of the virus much of the early research focused on the in vivo production and purification of the virus to obtain sufficient material to use to identify the viral proteins and purify the viral genetic material. Typically, new born lambs were inoculated intra-tracheally with concentrated lung lavage from previously infected sheep lungs. The optimal purification involved the concentration of lung ...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2001
The use of pyrazinamide (PZA) is important for the treatment of Mycobacterium tuberculosis as it ... more The use of pyrazinamide (PZA) is important for the treatment of Mycobacterium tuberculosis as it is bactericidal to semi-dormant mycobacteria that are not affected by other drugs. The incidence of resistance to PZA and other drugs used in the treatment of M. tuberculosis is increasing in South Africa. To characterise the pncA gene of M. tuberculosis isolates from Gauteng, South Africa, and to develop a rapid diagnostic method. The pncA gene and the putative regulatory gene were characterised by sequence analysis in a total of six PZA susceptible and 15 resistant isolates. The association with classical PZA susceptibility testing and PZase activity was determined. All PZA-resistant isolates were PZase negative as well as resistant to at least one other anti-tuberculosis drugs. Mutations were identified throughout the length of the pncA gene in 10/15 PZA-resistant isolates. Five lacked PZase activity, but the wild type pncA sequence was present. In all six PZase-positive strains, a PZ...
Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2000
Genotypic analysis of isoniazid (INH) resistance in 79 isolates of M. tuberculosis (MTB) was unde... more Genotypic analysis of isoniazid (INH) resistance in 79 isolates of M. tuberculosis (MTB) was undertaken by PCR-single strand conformation polymorphism (SSCP), Msp1 restriction enzyme analysis and sequence analysis of specific regions of three genes (part of the coding sequence of katG, and promoter regions of the inhA operon and ahpC) in order to determine the particular allelic variants within these genes. The epidemiologic relatedness was determined using IS6110 and polymorphic G-C region (PGRS (MTB484(1)) based restriction fragment length polymorphism (RFLP). Mutations in katG, inhA locus and ahpC were identified in 77/79, 19/79 and 10/79 isolates respectively. The ability of PCR-SSCP to detect mutations associated with INH resistance in katG, inhA and ahpC genes was 100% (CI 91.2-99.7%), 98.7% (CI 74.0-99.9%), and 100% (CI 69.2-100%) respectively. Specificity was 100%. All isolates with mutations in the 209 bp fragment of the MTB katG gene containing the Ser315Thr codon were pos...
Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung tumour of sheep ... more Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung tumour of sheep known as sheep pulmonary adenomatosis (syn: ovine pulmonary carcinoma, jaagsiekte). JSRV exhibits a simple genetic organization, characteristic of the type D and type B retroviruses, with the canonical retroviral sequences gag, pro, pol and env encoding the structural proteins of the virion. An additional open reading frame (orf-x), of approximately 500 bp overlapping pol, is present in the only two complete sequences of JSRV published to date. Since very little information is available on the biology of JSRV it is important to establish if orf-x is conserved between different virus isolates. In this study we analysed the orf-x region of JSRV isolates collected from the United Kingdom, Italy, Spain and South Africa. In addition we also analysed the presence of orf-x in JSRV-related endogenous sequences (enJSRVs) present in the sheep genome. Orf-x was highly conserved in all the exogenous...
The Veterinary clinics of North America. Food animal practice, 1997
As retrovirus-induced neoplasms of the respiratory epithelium of sheep and goats, OPC and ENT ran... more As retrovirus-induced neoplasms of the respiratory epithelium of sheep and goats, OPC and ENT rank as economically important diseases in many countries of the world. They are also important as models of retroviral carcinogenesis of the secretory epithelium of the respiratory system. Control of both diseases is dependent on development and application of sensitive and specific assays for identification of carrier animals infected with the causative agents of these diseases. Recent progress in characterization of type D/B retroviruses associated with the diseases and development of new reagents for the immunologic or molecular detection of antiviral antibodies, viral proteins, or viral nucleic acids bodes well for improved control or prevention of these diseases.
The Onderstepoort journal of veterinary research, 1986
In the course of attempts to grow the jaagsiekte retrovirus in cell culture, a typical lentivirus... more In the course of attempts to grow the jaagsiekte retrovirus in cell culture, a typical lentivirus was isolated for the first time in South Africa from adenomatous lungs. Morphologically the virus could not be distinguished from other lentiviruses, but serologically it was shown to be more closely related to visna virus than to caprine arthritis-encephalitis virus. However, a preliminary restriction enzyme analysis of the linear proviral DNA of this new lentivirus (SA-DMVV) revealed that it is significantly district from visna virus and CAEV and therefore may represent a third type of lentivirus. Antibodies to the virus were demonstrated in a number of sheep in various parts of the country, but a direct link to a disease condition was not found. Attempts to produce lung lesions by intratracheal injection of the virus have been unsuccessful to date but a transient arthritis was produced by intraarticular inoculation. Viral replication seems to be enhanced in jaagsiekte lungs.
The Onderstepoort journal of veterinary research, 1988
A South African isolate of ovine lentivirus was shown to cause a mild immunosuppression in sheep,... more A South African isolate of ovine lentivirus was shown to cause a mild immunosuppression in sheep, reflected by a reduced delayed hypersensitivity reaction. This effect, measured in terms of skin swelling after intradermal inoculation with tuberculin, showed a positive linear relationship with the latency period before the appearance of jaagsiekte symptoms in animals co-infected with JSRV, as well as with the activity of monocytes. In a parallel study, increased susceptibility of lentivirus-infected sheep to infection with Pasteurella haemolytica was demonstrated. It is concluded that the lentivirus may play an enhancing role in both viral and bacterial infections of sheep by compromising the host's cellular immune response.
The complete genome of the jaagsiekte sheep retrovirus (JSRV), the suspected etiological agent of... more The complete genome of the jaagsiekte sheep retrovirus (JSRV), the suspected etiological agent of ovine pulmonary carcinoma, has been cloned from viral particles secreted in lung exudates of affected animals and sequenced. The genome is 7,462 nucleotides long and exhibits a genetic organization characteristic of the type B and D oncoviruses. Comparison of the amino acid sequences of JSRV proteins with those of other retrovirus proteins and phylogenetic studies suggest that JSRV diverged from its type B and D lineage after the type B mouse mammary tumor virus but before the type D oncoviruses captured the env gene of a reticuloendotheliosislike virus. Southern blot studies show that closely related sequences are present in sheep and goat normal genomic DNA, indicating that JSRV could be endogenous in ovine and caprine species.
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