Host cell-specific growth advantage of pseudorabies virus with a deletion in the genome sequences encoding a structural glycoprotein

Abstract

Several attenuated strains of pseudorabies virus contain genomes that carry a deletion in their short unique (Us) component. The sizes of the deletions are different in the various attenuated strains; the deletions may include part of one of the inverted repeats as well as part of the Us region of the genome. In most cases, the deletion includes the gene encoding the glycoprotein gI. The attenuated strains with a deletion in their S component have a common history of having been cultivated in chicken embryo fibroblasts (CEF). We show here that passage of wild-type virus in CEF promotes the emergence of populations of virions with a deletion in their S component. The emergence of these mutants is the result of their growth advantage over the wild type and is related to the lack of expression of gI, as shown by the following. (i) The Norden strain (which has a deletion in the Us) was marker rescued to restore an intact Us. The nonrescued Norden strain had a growth advantage over the rescued Norden strain in CEF. (ii) Passage of wild-type (gI+) virus in CEF but not in rabbit kidney or pig kidney cells resulted invariably in the emergence of virions whose genomes had a deletion in the S component. (iii) Passage of a glmutant in CEF did not result in the emergence of such virions. The emergence of virions with a deletion in their S component thus appears to be linked to gI expression. We conclude that gI is deleterious to the growth of pseudorabies virus in CEF and that this effect is cell type specific.

Complex between glycoproteins gI and gp63 of pseudorabies virus: its effect on virus replication

“…Indeed, the yields of infectious virus and of viral particles obtained from RK and PK cells infected with gIor gp63deletion-M13 insertion mutants, with glor gp63-deletion mutants, or with wild-type virus are approximately the same (3, 13). Mutations in gI do, however, affect virus growth in a subtle way:-gF mutants of PrV have a small but definite growth advantage over PrV(Ka) in CEF (11). Since gI and gp63 are found in infected cell extracts in the form of a complex, it appeared possible that the two glycoproteins affect virus growth jointly.…”

“…Thus, some of these glycoproteins play a role in virulence, in adsorption, and in the release of virus from infected cells. Furthermore, they may affect virus growth in a cell-type-specific fashion (3,11,(13)(14)(15)23).…”

“…Both glycoproteins gI and gp63 also affect virulence, an effect that is also evident only in conjunction with a defect in glycoprotein gIll (as well as possibly in conjunction with a defect in some other viral function) (14,15). Furthermore, a defect in gI alone affects virus growth in a cell type-specific fashion; the absence of this glycoprotein confers upon PrV(Ka) a growth advantage in primary chicken embryo fibroblasts (CEF) but not in RK or pig kidney (PK) cells (11). In addition, glll has been shown to be involved in virus adsorption (23).…”

The Us9 Gene Product of Pseudorabies Virus, an Alphaherpesvirus, Is a Phosphorylated, Tail-Anchored Type II Membrane Protein

“…For instance, the vaccine strain Bartha (Ba) has a large Us deletion encompassing gI, gE, Us9 (the old nomenclature was 11K), and Us2 (the old nomenclature was 28K) (35,42,45). The attenuated strain Norden has a similar Us deletion including gI, gE, and Us9 (35,41,42). While it is generally accepted that the lack of the gI and gE genes accounts for most of the reduced virulence and tropism defects in these attenuated strains (1, 4-6, 19, 24, 25, 28, 36, 41, 42, 55, 66), it is not clear why Us9 or Us2 should be deleted in these natural isolates.…”

Studies on the immunoreactivity of native and recombinant pseudorabies virus nucleocapsid proteins

“…Functional studies indicate that gp63 and gl play major roles in the release of progeny virions from PRV infected cells (62,66,68,74), The host immune response to gp63 has not been described to date.…”