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Comparison of pathogenic properties of the murid gammaherpesvirus (MuHV 4) strains: a role for immunomodulatory proteins encoded by the left (5′-)end of the genome

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Central European Journal of Biology

Abstract

The murid herpesvirus 4 (MuHV 4) species encompasses 7 isolates, out of which at least two (MHV-68, MHV-72) became in vitro propagated laboratory strains. Following intranasal inoculation, MuHV 4 induces an acute infectious mononucleosis-like syndrome with elevated levels of peripheral blood leukocytes, shifts in the relative proportion of lymphocytes along with the appearance of atypical mononuclear cells. At least two isolates exhibited spontaneous deletions at the left hand (5′-end) of their genome, resulting in the absence of M1, M2, M3 genes (strain MHV-72) and also of the M4 gene (strain MHV-76). Based on DNA sequence amplifications only, another two isolates (MHV-Šum and MHV-60) were shown to possess similar deletions of varying length. During latency (until 24 months post-infection), the mice infected with any MuHV 4 isolate (except MHV-76) developed lymphoproliferative disorders. The lack of tumor formation in MHV-76 infected mice was associated with persistent virus production at late post-infection intervals. In addition to careful analysis of spontaneously occurring 5′-end genome defects, our knowledge of the function of 5′-end genes relies on the behaviour of mutants with corresponding deletions and/or insertions. While M2 and M3 genes encode immune evasion proteins, M4 codes for a soluble glycopeptide acting as immunomodulator and/or immunostimulator.

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Abbreviations

HSV:

herpes simplex virus

i.n.:

intranasal

i.p.:

intraperitoneal

p.i.:

post-infection

MHV:

mouse herpesvirus (murine gammaherpesvirus)

MuHV:

murid herpesvirus (official nomenclature)

PCR:

polymerase chain reaction

bp:

base pair

kb:

kilobase pair

nt(s):

nucleotide(s)

w.t.:

wild-type

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Mistríková, J., Rajčáni, J. Comparison of pathogenic properties of the murid gammaherpesvirus (MuHV 4) strains: a role for immunomodulatory proteins encoded by the left (5′-)end of the genome. cent.eur.j.biol. 3, 19–30 (2008). https://doi.org/10.2478/s11535-008-0002-0

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