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Virology. 2017 Jun;506:141-151. doi: 10.1016/j.virol.2017.03.012. Epub 2017 Apr 6.

The MVMp P4 promoter is a host cell-type range determinant in vivo.

Author information

1
Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
2
Departments of Laboratory Medicine and Genetics, Yale University School of Medicine, New Haven, CT, USA.
3
Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel. Electronic address: clay@bgu.ac.il.

Abstract

The protoparvovirus early promoters, e.g. P4 of Minute Virus of Mice (MVM), play a critical role during infection. Initial P4 activity depends on the host transcription machinery only. Since this is cell-type dependent, it is hypothesized that P4 is a host cell-type range determinant. Yet host range determinants have mapped mostly to capsid, never P4. Here we test the hypothesis using the mouse embryo as a model system. Disruption of the CRE element of P4 drastically decreased infection levels without altering range. However, when we swapped promoter elements of MVM P4 with those from equivalent regions of the closely related H1 virus, we observed elimination of infection in fibroblasts and chondrocytes and the acquisition of infection in skeletal muscle. We conclude that P4 is a host range determinant and a target for modifying the productive infection potential of the virus - an important consideration in adapting these viruses for oncotherapy.

KEYWORDS:

Autonomous parvovirus; Host-range determinant; MVM; P4 promoter; Protoparvovirus; Viral transcription

PMID:
28391161
DOI:
10.1016/j.virol.2017.03.012
[Indexed for MEDLINE]
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