The capsid determinant of fibrotropism for the MVMp strain of minute virus of mice functions via VP2 and not VP1

Abstract

The minute virus of mice, prototype strain MVMp, productively infects cultured murine fibroblasts but not T cells. The immunosuppressive strain, MVMi, shows the converse tropism. These reciprocal tropisms are mediated by the viral capsids, in which their determinants have been mapped to a few specific amino acids in the primary sequence shared by VP1 and VP2. Which of these proteins is relevant in presenting these determinants during infection is not known. We have approached this question using a recombinant parvovirus system in which a LuIII-derived transducing genome, containing the luciferase reporter in place of viral coding sequences, can be packaged by capsid proteins from separate helper sources. We generated transducing virions by using helper constructs expressing either VP1 or VP2, containing the MVMp or MVMi tropic determinant region, in various combinations. The virions were used to infect human NB324K cells and murine A9 fibroblasts. Transduction of the human cells (permissive for both MVMp and MVMi) required both VP1 and VP2 and was successful with all combinations of these proteins. In contrast, significant transducing activity for A9 cells was detected only with recombinant virions containing VP2 of MVMp, while the use of either source of VP1 had little effect. We conclude that VP2 from MVMp is necessary to enable infection of murine A9 fibroblasts.

Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition

“…This similarity in glycan profile thus fails to explain the differences in tropism for these cells between these MVM viruses based on differential cell surface glycan receptor recognition. These observations support previous claims that the determinant of differential cell and tissue tropism for MVMp and MVMi is post cell entry [26,28,36,58,59]. These previous reports identified amino acids at and surrounding the depression at icosahedral 2-fold axes of the capsid, which differ between the viruses, as playing a crucial role in dictating these differences.…”

Identification of novel murine parvovirus strains by epidemiological analysis of naturally infected mice

“…Many of these regions of diversity corresponded to regions that are located at or near the surface of the capsid, as determined by extrapolation from the threedimensional structure of MVMi (Agbandje-McKenna et al, 1998;Llamas-Saiz et al, 1997). These differences in the capsid region could alter tissue tropism and haemagglutination, and ultimately in vivo pathogenesis, displayed by the newly identified murine parvovirus strains, as has been shown for MVMi and MVMp (Agbandje-McKenna et al, 1998;Ball-Goodrich & Tattersall, 1992;Brownstein et al, 1991Brownstein et al, , 1992Kimsey et al, 1986;Maxwell et al, 1995) and for the Feline parvovirus subgroup (Chang et al, 1992;Govindasamy et al, 2003;Parker & Parrish, 1997;Parrish, 1991;Tresnan et al, 1995;Tsao et al, 1991).…”

Construction and initial characterization of an infectious plasmid clone of a newly identified hamster parvovirus

“…An intracellular particle-mediated block has been previously described for MVMi in A9 cells (Gardiner & Tattersall, 1988 a ). The different tissue tropisms of MVMi and MVMp do not depend on cellular receptors (Spalholz & Tattersall, 1983 ; Tattersall & Bratton, 1983 ) but rather on some virus- and cell-specific intracellular factors interacting either directly or indirectly with a region of the viral capsid protein VP2, termed the allotropic determinant (Gardiner & Tattersall, 1988 b ; Ball-Goodrich & Tattersall, 1992 ; Maxwell et al , 1995 ). The basis for the described restriction of HaPV in murine cells is similar and is probably due to some combination of the subtle differences between the HaPV and MVMp capsids.…”