Partial dissociation of subgroup C phenotype and in vivo behaviour in feline leukaemia viruses with chimeric envelope genes

Rigby, Mark A.; Rojko, Jennifer L.; Stewart, Monica; Kociba, Gary J.; Cheney, Carolyn; Rezanka, Louis J.; Mathes, Lawrence E.; Hartke, James R.; Jarrett, Oswald; Neil, James C.

doi:10.1099/0022-1317-73-11-2839

Cited by 61 publications

(67 citation statements)

References 32 publications

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“…FLVCR1 function was disrupted by expression of the envelope (Env) protein from the subgroup C feline leukemia virus (FeLV-C). Previous studies showed that FeLV-C infection of target cells disrupts both subsequent FeLV-C virus infection 28,38 and FLVCR1 heme export, 30 which led to the hypothesis that the FeLV-C Env protein disrupts FLVCR1. To show that FeLV-C Env specifically disrupts human FLVCR1, we expressed FeLV-C Env in human TE671 cells.…”

Section: Disruption Of Human Flvcr1 Affects Erythropoiesis But Not Mymentioning

confidence: 99%

“…[21][22][23] The feline anemia has been suggested to be caused by the FeLV-C envelope (Env) protein disrupting the cellular function of the heme exporter FLVCR1, 24 which is used as a receptor for entry by FeLV-C. [25][26][27][28][29] Disruption of FLVCR1 heme export function in human K562 erythroid cells induces apoptosis and disrupts K562 erythroid differentiation. 30 Furthermore, FLVCR1 null mice, despite dying in utero and having reduced levels of myeloid and lymphoid cells, 31 show a severe disruption in the development of erythroid colonyforming units (CFU-E), and have the craniofacial and limb deformities found in some DBA patients.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis

Rey¹,

Duffy²,

Brown³

et al. 2008

Haematologica

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Section: Disruption Of Human Flvcr1 Affects Erythropoiesis But Not Mymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis

Rey¹,

Duffy²,

Brown³

et al. 2008

Haematologica

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“…Receptor specificity and binding of the viral Envelope (Env) is mapped to the N-terminal half of the surface (SU) protein through the close interaction of two highly variable regions, VR1 (VRA) and VR2 (VRB) (14-18). Exchange of a defined VR1 segment between the FeLV A and C subgroups altered the viral host range (19). In our studies, codons for 10/11 amino acids within this VR1 FeLV Env receptor-binding region were randomized within a FeLV A/C Env chimera backbone (20).…”

mentioning

confidence: 99%

Identification of a retroviral receptor used by an Envelope protein derived by peptide library screening

Sarangi¹,

Bupp²,

Roth³

2007

Proc. Natl. Acad. Sci. U.S.A.

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(11)(12)(13)] viral receptors. With these evolutionary observations, it is of great interest as to whether a given retrovirus must remain restricted to use receptors within the broad class of the original receptor or can be altered to use receptors beyond these protein family boundaries.A variety of approaches have been developed for altering the receptor usage of viral delivery systems. Receptor specificity and binding of the viral Envelope (Env) is mapped to the N-terminal half of the surface (SU) protein through the close interaction of two highly variable regions, VR1 (VRA) and VR2 (VRB) (14-18). Exchange of a defined VR1 segment between the FeLV A and C subgroups altered the viral host range (19). In our studies, codons for 10/11 amino acids within this VR1 FeLV Env receptor-binding region were randomized within a FeLV A/C Env chimera backbone (20). Viral particles bearing this library of Ͼ1 million viral VR1 Env variants are selected for productive infection (20)(21)(22). This library displays the targeting peptide within the context of the authentic Env backbone, eliminating the problem that preidentified phage display peptides inserted into alternative contexts do not maintain their original properties (23). Alternative approaches have involved the addition of targeting domains (24, 25), peptides (23, 26), or single-chain antibodies (27) within the framework of viral Env or capsids (28-30) or through heterologous intermediates (31). Successful retargeting for Sindbis Env pseudotyped onto lentiviral particles has been achieved with the insertion of the Protein A ZZ domain and sandwiching targeting antibodies to the modified particles (32) or through coexpression of Env proteins and surfacebinding molecules (33).Screening the FeLV random Env library on feline AH927 cells identified the A5 Env isolate, which also efficiently infected human 293T embryonic kidney cells (21). Superinfection interference studies indicated that the receptor for A5 was outside the receptor family used by FeLV A, B, and C and MuLV 4070A viruses (21). The A5 Env therefore provided an excellent system to examine the range of proteins capable of serving as receptors for retroviral Env libraries. In this study, the receptor for the A5 Env isolate was identified as the SLC35F2 protein, a transporter protein of unknown function, through screening a feline AH927 cDNA library. ResultsDirected evolution allows for the selection of proteins with new properties. Using this approach, randomization of the FeLV Env receptor-binding domain, followed by selection for productive infection, identified Env isolates with receptor usage outside the interference groups of the known FeLV A, B, and C viruses (21,22). This result implies that the selection of a receptor protein can occur through screening a single round of viral infection. To definitively prove that alternative viral receptors can be selected, the receptor protein for the A5 Env isolate was identified through cDNA screening. The authors declare no conflict of interest.Abbreviations: Env,...

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“…Subgroups B and D arose from the recombination of FeLV-A env and the env genes of endogenous FeLV or endogenous retroviruses in the genomes of domestic cats (ERV-DCs) (7, 9, 10). Subgroups C and T possibly arose from mutations in FeLV-A env (11,12). The recombination or mutation of env often alters the interference and host ranges of FeLVs by affecting their receptor usage (5,6,13,14,15,16).…”

mentioning

confidence: 99%

Novel Feline Leukemia Virus Interference Group Based on the env Gene

Miyake

Watanabe

Hiratsuka

et al. 2016

J Virol

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cFeline leukemia virus (FeLV) subgroups have emerged in infected cats via the mutation or recombination of the env gene of subgroup A FeLV (FeLV-A), the primary virus. We report the isolation and characterization of a novel env gene, TG35-2, and report that the TG35-2 pseudotype can be categorized as a novel FeLV subgroup. The TG35-2 envelope protein displays strong sequence identity to FeLV-A Env, suggesting that selection pressure in cats causes novel FeLV subgroups to emerge. Feline leukemia viruses (FeLVs) are pathogenic retroviruses of domestic cats (1, 2), which are classified into subgroups A (the parent virus), B, C, D, and T based on their interference and in vitro host range properties (3,4,5,6,7,8). Subgroups B and D arose from the recombination of FeLV-A env and the env genes of endogenous FeLV or endogenous retroviruses in the genomes of domestic cats (ERV-DCs) (7, 9, 10). Subgroups C and T possibly arose from mutations in FeLV-A env (11,12). The recombination or mutation of env often alters the interference and host ranges of FeLVs by affecting their receptor usage (5,6,13,14,15,16).FeLV env genes were isolated by PCR from the blood DNA of a 1-year-old castrated male cat, TG35, with a bite injury, stomatitis, loss of appetite, and FeLV infection, although he had been vaccinated with inactivated FeLV (genotype III) (16). Five clones (TG35-1 to -5) were isolated, and we focused on TG35-2, TG35-4, and TG35-5. The env sequences of these clones showed strong similarity ( Fig. 1), and the viruses clustered phylogenetically with those of genotype I/clade I FeLV, found mainly in Japan (16). The encompassing variable region A (VRA) of TG35-2 Env differs at eight amino acids from those of the TG35-4 and TG35-5 Env proteins. The proline-rich regions of TG35-2 and TG35-4, but not TG35-5, contain an inserted sequence of 25 amino acids (Fig. 1) not found in the cat genome database and of unknown origin.To identify the FeLV subgroup to which this viral strain belongs, we used an interference assay (16) and generated ␤-galactosidase (LacZ)-encoding pseudotype viruses expressing TG35-2, TG35-4, or TG35-5 envelope (Env) proteins in GPLac cells (7). Pseudotype viruses TG35-2, -4, and -5 infected uninfected HEK293T cells (Table 1). However, HEK293T cells preinfected with FeLV-A/clone 33 (293T/clone 33 cells) (17) or FeLV-A/Glasgow-1 (293T/Glasgow-1 cells) (9) were infected by pseudotype virus TG35-2, but not by TG35-4 or TG35-5. Neither cell type was infected by FeLV-A/clone 33 or FeLV-A/Glasgow-1. Therefore, only the TG35-4 and TG35-5 viruses interfered with FeLV-A. Neither the TG35-2, TG35-4, nor TG35-5 pseudotype interfered with other subgroups of FeLV, or with retroviruses such as ERV-DC10, a replication-competent feline ERV (7) ( Table 1). Therefore, FeLV TG35-4 and TG35-5 belong to the FeLV-A subgroup. However, TG35-2 could not be categorized.We next constructed a replication-competent virus (33TGE2) containing the TG35-2 env gene and the LTR, gag, and pol genes of When we examined AH927 feline cells, the TG35-2...

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Partial dissociation of subgroup C phenotype and in vivo behaviour in feline leukaemia viruses with chimeric envelope genes

Cited by 61 publications

References 32 publications

Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis

Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis

Identification of a retroviral receptor used by an Envelope protein derived by peptide library screening

Novel Feline Leukemia Virus Interference Group Based on the env Gene

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