Cell-binding properties of the envelope proteins of porcine endogenous retroviruses

Watanabe, Rie; Miyazawa, Takayuki; Matsuura, Yoshiharu

doi:10.1016/j.micinf.2005.01.008

Cited by 22 publications

(18 citation statements)

References 40 publications

(26 reference statements)

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“…In ecotropic and amphotropic murine leukaemia viruses, the receptor-binding domain needed for binding with host receptors spans VRA and VRB. In PERV-A and PERV-B, PRR might be involved in the proper binding to their receptors together with VRA and VRB (Watanabe et al, 2005). Recently, it was revealed that CR was also important for the infectivities of PERV-A and PERV-C (Gemeniano et al, 2006;Argaw et al, 2008).…”

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confidence: 99%

“…PERV SU Env consists of four subdomains, known as variable regions A and B (VRA and VRB), proline-rich region (PRR) and the C-terminal region (CR). Of these domains, VRA, VRB and PRR are divergent between subgroups (Le Tissier et al, 1997;Watanabe et al, 2005). In ecotropic and amphotropic murine leukaemia viruses, the receptor-binding domain needed for binding with host receptors spans VRA and VRB.…”

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confidence: 99%

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Mapping of a neutralizing epitope in the surface envelope protein of porcine endogenous retrovirus subgroup B

Nakaya

Hoshino

Yasuda

et al. 2011

Journal of General Virology

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Pigs are thought to be the most suitable donor animal for xenotransplantation. However, pigs harbour potentially hazardous infectious agents, termed porcine endogenous retroviruses (PERVs), in their genome. In this study, we generated a mAb against PERV-B surface (SU) envelope protein (Env), designated KRT1. KRT1 binding was detected by an indirect immunofluorescence assay and flow cytometric analysis on cells infected with PERV-B. KRT1 neutralized PERV-B pseudotype virus and specifically recognized PERV-B SU Env, but not PERV-A SU Env by immunoblotting analysis. The peptide-ELISA revealed that KRT1 recognized a linear peptide sequence (ALEPPHNLPVP) residing in a proline-rich region that is one of the subdomains of SU Env. In conclusion, the KRT1 antibody will serve as a useful tool for the study of PERV-B and, more importantly, it may provide new protective strategies against PERV-B infection in xenotransplantation.Xenotransplantation is a solution to the shortage of human donors, and pigs are considered as the most suitable donor animal (Blusch et al., 2002). Although specific-pathogenfree pigs will be used for xenotransplantation, all pigs possess potentially hazardous infectious viral agents, named porcine endogenous retroviruses (PERVs), in their genome (Blusch et al., 2002). PERVs are members of the genus Gammaretrovirus and are divided into three subgroups (termed PERV-A, PERV-B and PERV-C) based on their different receptor usages (Le Tissier et al., 1997;Patience et al., 1997;Denner, 2008). PERV-A and PERV-B may transmit from pigs to humans, because humans have functional receptors for both PERV-A and PERV-B (Takeuchi et al., 1998;Denner, 2008). Although the risks caused by the infection with PERVs have not been fully assessed at present, they may potentially cause leukaemia, anaemia, immunodeficiency and cancers like other gammaretroviruses (Kawakami et al., 1980;Wilson et al., 2000;Denner, 2008). Gammaretroviral envelope (Env) consists of surface (SU) and transmembrane (TM) subunits, which interact via a disulfide bond between SU CX 2 C-and TM CX 7 C-motifs (Wallin et al., 2004). PERV SU Env consists of four subdomains, known as variable regions A and B (VRA and VRB), proline-rich region (PRR) and the C-terminal region (CR). Of these domains, VRA, VRB and PRR are divergent between subgroups (Le Tissier et al., 1997;Watanabe et al., 2005). In ecotropic and amphotropic murine leukaemia viruses, the receptor-binding domain needed for binding with host receptors spans VRA and VRB. In PERV-A and PERV-B, PRR might be involved in the proper binding to their receptors together with VRA and VRB (Watanabe et al., 2005). Recently, it was revealed that CR was also important for the infectivities of PERV-A and PERV-C (Gemeniano et al., 2006;Argaw et al., 2008).The information about the antigenicity of PERV Env is quite limited (Chiang et al., 2007) and the antigenic property of PERV-B Env has not yet been reported. In this study, we generated a neutralizing mAb against PERV-B and determined the neutralizing epitop...

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confidence: 99%

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confidence: 99%

Mapping of a neutralizing epitope in the surface envelope protein of porcine endogenous retrovirus subgroup B

Nakaya

Hoshino

Yasuda

et al. 2011

Journal of General Virology

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“…The retroviral Env SU subunit is utilized for receptor recognition, and the conformation of SU and its receptor usage depend on retroviral species (30,31). Currently, it is unclear whether Fematrin-1 and BERV-K2 Env recognize the same receptor; however, we previously reported that they both could bind Cos-7 cells at a similar level (14).…”

Section: Discussionmentioning

confidence: 94%

Dysfunction of Bovine Endogenous Retrovirus K2 Envelope Glycoprotein Is Related to Unsuccessful Intracellular Trafficking

Nakaya

Miyazawa

2014

J Virol

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Endogenous retroviruses (ERVs) are the remnants of retroviral infection of ancestral germ cells. Mutations introduced intoERVs halt the production of infectious agents, but their effects on the function of retroviral proteins are not fully understood. Retroviral envelope glycoproteins (Envs) are utilized in membrane fusion during viral entry, and we recently identified intact coding sequences for bovine endogenous retrovirus K1 (BERV-K1) and BERV-K2 Envs. Amino acid sequences of BERV-K1 Env (also called Fematrin-1) and BERV-K2 Env are similar, and both viruses are classified in the genus Betaretrovirus. While Fematrin-1 plays an important role in cell-to-cell fusion in bovine placenta, the BERV-K2 envelope gene is marginally expressed in vivo, and its recombinant Env protein is defective in membrane fusion due to inefficient cleavage of surface (SU) and transmembrane subunits. Here, we conducted chimeric analyses of Fematrin-1 and BERV-K2 Envs and revealed that defective maturation of BERV-K2 Env contributed to failed intracellular trafficking. Fluorescence microscopy and flow cytometric analysis suggested that in contrast to Fematrin-1 Env, BERV-K2 Env could not be transported from the endoplasmic reticulum to the trans-Golgi network, where cellular proteases required for processing retroviral Envs are localized. We also identified that one of the responsive regions of this phenomenon resided within a 65-amino-acid region of BERV-K2 SU. This is the first report to identify that retroviral Env SU is involved in the regulation of intracellular trafficking, and it may help to elucidate the maturation process of Fematrin-1 and other related Envs. IMPORTANCERetroviruses utilize envelope glycoproteins (Envs) to enter host target cells. Mature retroviral Env is a heterodimer, which consists of surface (SU) and transmembrane (TM) subunits that are generated by the cleavage of an Env precursor protein in the trans-Golgi network. SU and TM mediate the recognition of the entry receptor and virus-host membrane fusion, respectively. However, unexplained issues remain for the maturation process of retroviral Env. We previously reported that bovine endogenous retrovirus K2 (BERV-K2) Env lost fusogenicity due to a defect in the cleavage of SU and TM. In this study, we identified that mutations residing in BERV-K2 SU disturbed intracellular trafficking of BERV-K2 Env and resulted its inefficient cleavage. Because SU is not known to play an important role in this process, our study may provide novel insights into the maturation mechanism of retroviral Envs.

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“…Interestingly, PERV-A and PERV-C SU either differ slightly or agree in their dibasic proteolytic cleavage signal sequence. Depending on the cDNA isolates of the PERV-C envelope from porcine cells, the PERV-C sequence at the C terminus of SU has been reported as either R-Q-KR (1,38) or R-Q-KK (13, 17) (here and GenBank accession numbers DQ996276.1 and AF402663.1), while the corresponding residues reported in PERV-A have always been observed as R-P-KR (1,23,50,53). The use of KK versus KR appears to be unique to …”

Section: Discussionmentioning

confidence: 99%

“…Additional determinants that are important for viral entry have been found in both the amino and carboxyl regions of gammaretroviral SU (3,5,18,21,22,32). Although the in vitro host range of PERV envelope classes has been studied (46,53), more detailed mapping of determinants within the envelope that are critical to human cell infection by PERV has just begun (13,16,50).…”

mentioning

confidence: 99%

Identification of Residues outside of the Receptor Binding Domain That Influence the Infectivity and Tropism of Porcine Endogenous Retrovirus

Argaw

Figueroa

Salomon

et al. 2008

J Virol

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Cell-binding properties of the envelope proteins of porcine endogenous retroviruses

Cited by 22 publications

References 40 publications

Mapping of a neutralizing epitope in the surface envelope protein of porcine endogenous retrovirus subgroup B

Mapping of a neutralizing epitope in the surface envelope protein of porcine endogenous retrovirus subgroup B

Dysfunction of Bovine Endogenous Retrovirus K2 Envelope Glycoprotein Is Related to Unsuccessful Intracellular Trafficking

Identification of Residues outside of the Receptor Binding Domain That Influence the Infectivity and Tropism of Porcine Endogenous Retrovirus

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