Dataset Information

Species-specific differences in the structure of orthopoxvirus complement-binding protein.

ABSTRACT: Vaccinia virus complement-binding protein (VCP) is secreted from the cells infected with the virus and controls the complement activation reactions. This protein contains four short consensus repeats (SCR), typical of the protein family of complement activation regulators. Organization of the VCP genes/proteins of orthopoxviruses-monkeypox (MPV), variola, cowpox and vaccinia viruses-and their cellular homologues (DAF and C4BP) were studied comparatively. For this purpose, VCP genes of three MPV strains were sequenced. VCP gene sequences of other human-pathogenic orthopoxvirus species and strains determined earlier were involved in the analysis. It has been demonstrated that a premature termination of the MPV VCP open reading frame results in a truncated protein sequence carrying a deletion of the C-terminal SCR4. This is an essential distinction of MPV from other orthopoxvirus species.

SUBMITTER: Uvarova EA

PROVIDER: S-EPMC9629043 | biostudies-literature | 2001 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Species-specific differences in the structure of orthopoxvirus complement-binding protein.

Uvarova E A EA Shchelkunov S N SN

Virus research 20011201 1-2

Vaccinia virus complement-binding protein (VCP) is secreted from the cells infected with the virus and controls the complement activation reactions. This protein contains four short consensus repeats (SCR), typical of the protein family of complement activation regulators. Organization of the VCP genes/proteins of orthopoxviruses-monkeypox (MPV), variola, cowpox and vaccinia viruses-and their cellular homologues (DAF and C4BP) were studied comparatively. For this purpose, VCP genes of three MPV ...[more]

PMID: 11682123

Similar Datasets

Project description:The complement system plays a key role in opsonization and immune clearance of engineered nanoparticles. Understanding the efficiency, inter-subject, and inter-strain differences of complement opsonization in preclinical species can help with translational nanomedicine development and improve our ability to model complement response in humans. Dextran-coated superparamagnetic iron oxide (SPIO) nanoparticles and a wide range of non-magnetic iron oxide nanoparticle formulations are widely used in magnetic resonance imaging and as clinically approved iron supplements. Previously we found that opsonization of SPIO nanoworms (NW) with the third complement protein (C3) proceeds mostly via the alternative pathway in humans, and via the lectin pathway in mice. Here, we studied the pathway and efficiency of opsonization of 106 nm SPIO NW with C3 in different preclinical species and commonly used laboratory strains. In sera of healthy human donors (n = 6), C3 opsonization proceeded exclusively through the alternative pathway. On the other hand, the C3 opsonization in dogs (6 breeds), rats (4 strains) and mice (5 strains) sera was either partially or completely dependent on the complement Ca2+-sensitive pathways (lectin and/or classical). Specifically, C3 opsonization in sera of Long Evans rat strain, and mouse strains widely used in nanomedicine research (BALB/c, C57BL/6 J, and A/J) was only through the Ca2+-dependent pathways. Dogs and humans had the highest between-subject variability in C3 opsonization levels, while rat and mouse sera showed the lowest between-strain variability. Furthermore, using a panel of SPIO nanoparticles of different sizes and dextran coatings, we found that the level of C3 opsonization (C3 molecules per milligram Fe) in human sera was lower than in animal sera. At the same time, there was a strong predictive value of complement opsonization in dog and rat sera; nanoparticles with higher C3 deposition in animals showed higher deposition in humans, and vice versa. Notably, the opsonization decreased with decreasing size in all sera. The studies highlight the importance of the consideration of species and strains for predicting human complement responses (opsonization) towards nanomedicines.

Dataset Information

Species-specific differences in the structure of orthopoxvirus complement-binding protein.

Publications

Species-specific differences in the structure of orthopoxvirus complement-binding protein.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets