Different impact of bovine complement regulatory protein 46 (CD46bov) as a cellular receptor for members of the species Pestivirus H and Pestivirus G

The chondrocytes in human articular cartilage from subjects of all ages express mRNAs for both of the aggregating proteoglycans aggrecan and versican, although the level of expression of versican mRNA is much lower than that of aggrecan mRNA. Aggrecan shows alternative splicing of the epidermal growth factor (EGF)-like domain within its C-terminal globular region, but there is no evidence for a major difference in situ in the relative expression of this domain with age. At all ages studied from birth to the mature adult, a greater proportion of transcripts lacked the EGF domain. The relative proportions of the two transcripts did not change upon culture and passage of isolated chondrocytes. In contrast, the neighbouring complement regulatory protein (CRP)-like domain was predominantly expressed irrespective of age, but cell culture did result in variation of the splicing of this domain. Versican possesses two EGF-like domains and one CRP-like domain, but at all ages the three domains were predominantly present in all transcripts. This situation persisted upon culture and passage of the chondrocytes. Thus, unlike aggrecan, the versican expressed by human articular cartilage does not appear to undergo alternative splicing of its C-terminal globular region, either in cartilage in situ or in chondrocytes in culture.

Download Full-text

Complement Regulatory Protein Factor H Is a Soluble Prion Receptor That Potentiates Peripheral Prion Pathogenesis

The Journal of Immunology ◽

10.4049/jimmunol.1701100 ◽

2017 ◽

Vol 199 (11) ◽

pp. 3821-3827 ◽

Cited By ~ 4

Author(s):

Sarah J. Kane ◽

Taylor K. Farley ◽

Elizabeth O. Gordon ◽

Joshua Estep ◽

Heather R. Bender ◽

...

Keyword(s):

Regulatory Protein ◽

Factor H ◽

Complement Regulatory Protein ◽

Protein Factor

Download Full-text

The role of rat Crry, a complement regulatory protein, in proliferation of thymocytes

Life Sciences ◽

10.1016/j.lfs.2004.06.007 ◽

2004 ◽

Vol 75 (25) ◽

pp. 3053-3062 ◽

Cited By ~ 5

Author(s):

Jelena Antic Stankovic ◽

Dragana Vucevic ◽

Ivana Majstorovic ◽

Sasa Vasilijic ◽

Miodrag Colic

Keyword(s):

Regulatory Protein ◽

Complement Regulatory Protein

Download Full-text

Cytolytic assessment of hyperacute rejection and production of nuclear transfer embryos using hCD46-transgenic porcine embryonic germ cells

Zygote ◽

10.1017/s096719940800511x ◽

2009 ◽

Vol 17 (2) ◽

pp. 101-108 ◽

Cited By ~ 5

Author(s):

Ji Young Won ◽

Kwang Sung Ahn ◽

Alice M. Sorrell ◽

Susa Shin ◽

Soon Young Heo ◽

...

Keyword(s):

Nuclear Transfer ◽

Regulatory Protein ◽

Blastocyst Stage ◽

Hyperacute Rejection ◽

Complement Regulatory Protein ◽

Transgenic Pigs ◽

Embryonic Germ Cells ◽

Transgenic Embryos ◽

Stage Analysis ◽

Human Xenotransplantation

SummaryHuman complement regulatory protein hCD46 may reduce the hyperacute rejection (HAR) in pig-to-human xenotransplantation. In this study, an hCD46 gene was introduced into porcine embryonic germ (EG) cells. Treatment of human serum did not affect the survival of hCD46-transgenic EG cells, whereas the treatment significantly reduced the survival of non-transgenic EG cells (p < 0.01). The transgenic EG cells presumably capable of alleviating HAR were transferred into enucleated oocytes. Among 235 reconstituted oocytes, 35 (14.9%) developed to the blastocyst stage. Analysis of individual embryos indicated that 80.0% (28/35) of embryos contained the transgene hCD46. The result of the present study demonstrates resistance of hCD46-transgenic EG cells against HAR, and the usefulness of the transgenic approach may be predicted by this cytolytic assessment prior to actual production of transgenic pigs. Subsequently performed EG cell nuclear transfer gave rise to hCD46-transgenic embryos. Further study on the transfer of these embryos to recipients may produce hCD46-transgenic pigs.

Download Full-text

Porcine complement regulatory protein CD46 is a major receptor for atypical porcine pestivirus but not for classical swine fever virus

Journal of Virology ◽

10.1128/jvi.02186-20 ◽

2021 ◽

Author(s):

Gökce Nur Cagatay ◽

Aleksandra Antos ◽

Oliver Suckstorff ◽

Olaf Isken ◽

Norbert Tautz ◽

...

Keyword(s):

Classical Swine Fever Virus ◽

Regulatory Protein ◽

Classical Swine Fever ◽

Fever Virus ◽

Bovine Viral Diarrhea ◽

Complement Regulatory Protein ◽

Diarrhea Virus ◽

Viral Diarrhea ◽

Viral Diarrhea Virus ◽

Entry Mechanism

Pestiviruses such as bovine viral diarrhea virus (BVDV) and classical swine fever virus (CSFV) belong to the family Flaviviridae and represent pathogens of outstanding veterinary relevance. Pestiviruses enter cells via receptor-mediated endocytosis. For entry in bovine cells, complement regulatory protein CD46bov serves as cellular receptor for BVDV. In this study, the role of porcine CD46pig in cellular entry was investigated for the recently discovered atypical porcine pestivirus (APPV), CSFV, and Bungowannah virus (BuPV) in order to elucidate the observed differences in host cell tropism. A cell culture adapted APPV variant, which shows enhanced viral replication in vitro, was generated and demonstrated a strict tropism of APPV for porcine cells. One of the porcine cell lines displayed areas of CD46pig expressing and areas of non-expressing cells and one single cell line revealed not to express any CD46pig, respectively. The CD46pig deficient porcine lymphoma cells, known to facilitate CSFV replication, was the only porcine cell line non-permissive to APPV, indicating a significant difference in the entry mechanism of APPV and CSFV. Infection experiments with a set of genetically engineered CD46pig knockout cells confirmed that CD46pig is a major receptor of APPV as CD46bov is for BVDV. In contrast, it is apparently not an essential determinant in host cell entry of other porcine pestiviruses such as CSFV and BuPV. Existence of a CD46pig independent entry mechanism illustrates that the pestiviral entry process is more diverse than previously recognized. IMPORTANCE Pestiviruses comprise animal pathogens such as classical swine fever virus (CSFV) and bovine viral diarrhea virus (BVDV) that cause notifiable diseases with great economic impact. Several additional pestivirus species affecting animal health were recently identified, including atypical porcine pestivirus (APPV). APPV is associated with health problems in piglets and highly abundant in pig populations worldwide. Complement control protein CD46 serves as a receptor for diverse bacterial and viral pathogens, including particular adenoviruses, herpesviruses, measles virus (MeV), and BVDV. Porcine CD46 (CD46pig) was suggested to be a major receptor for CSFV. Here, we identified remarkable differences in relevance of CD46pig during entry of porcine pestiviruses. Resembling BVDV, efficient APPV infection in cell culture depends on CD46pig, while other porcine pestiviruses can efficiently enter and infect cells in absence of CD46pig. Thus, the study provides insights into the entry process of these pathogens and may help to understand differences in their biology.

Download Full-text