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Functional implications of the structure of the murine parvovirus, minute virus of mice
M Agbandje-McKenna1, A L Llamas-Saiz, F Wang
1Department of Biological Sciences, Purdue University, West Lafayette IN 47907-1392, USA.
Background:
Minute virus of mice (MVM) is a single-stranded (ss) DNA-containing, murine parvovirus with a capsid built up of 60 icosahedrally related polypeptide chains, each of which consists of the C-terminal region common to two structural proteins, VP1 and VP2. In infectious virions, most VP2 molecules are cleaved to VP3 by the removal of about 20 amino acids from the N terminus. Of the 587 amino acids in VP2, approximately half are identical to those in the analogous capsid protein of the antigenically distinct canine parvovirus (CPV), the crystal structure of which has previously been determined. The three-dimensional structure determination of MVMi (the immunosuppressive strain of MVM) was previously reported to 3.5 A resolution.
Results:
We report here an analysis of the MVMi virus structure and provide insights into tissue tropism, antigenicity and DNA packaging. Amino acids determining MVM tissue tropism were found to cluster on, or near, the viral surface. A conserved, glycine-rich, N-terminal peptide was seen to run through a cylindrical channel along each fivefold axis and may have implications for antigenicity. Density within the virion was interpreted as 29 ssDNA nucleotides per icosahedral asymmetric unit, and accounts for over one-third of the viral genome.
Conclusions:
The presence of the glycine-rich sequence in the fivefold channels of MVMi provides a possible mechanism to explain how the unique N-terminal region of VP1 becomes externalized in infectious parvovirions. Residues that determine tropism may form an attachment recognition site for a secondary host-cell factor that modulates tissue specificity. The ordering of nucleotides in a similar region of the interior surface in the CPV and MVMi capsids suggests the existence of a genomic DNA-recognition site within the parvoviral capsid.
Insights
Minute virus of mice (MVM) structure reveals key insights into its tissue tropism and antigenicity. The glycine-rich sequence in MVMi may explain VP1 externalization and DNA packaging.
Area of Science:
- Structural biology
- Virology
- Molecular biology
Background:
- Minute virus of mice (MVM) is a ssDNA parvovirus with an icosahedral capsid composed of VP1 and VP2 proteins.
- VP2 undergoes N-terminal cleavage to VP3 in infectious virions.
- MVM shares approximately 50% sequence identity with canine parvovirus (CPV) capsid protein.
Purpose of the Study:
- To analyze the MVMi virus structure and understand its tissue tropism, antigenicity, and DNA packaging.
- To investigate the role of specific amino acids and structural features in MVM's biological properties.
Main Methods:
- Three-dimensional structure determination of MVMi (previously reported to 3.5 A resolution).
- Analysis of viral surface amino acids and internal structural features.
Main Results:
- Amino acids determining MVM tissue tropism are located on or near the viral surface.
- A conserved glycine-rich peptide runs through fivefold channels, potentially influencing antigenicity.
- ssDNA nucleotides (29 per icosahedral asymmetric unit) were detected within the virion, constituting over one-third of the genome.
Conclusions:
- The glycine-rich sequence in MVMi's fivefold channels may facilitate the externalization of the VP1 N-terminal region.
- Tropism-determining residues could act as an attachment site for host-cell factors, modulating tissue specificity.
- Nucleotide ordering within MVMi and CPV capsids suggests a conserved genomic DNA-recognition site in parvoviruses.