An African swine fever virus ERV1-ALR homologue, 9GL, affects virion maturation and viral growth in macrophages and viral virulence in swine

T. Lewis, L. Zsak, T. G. Burrage, Z. Lu, G. F. Kutish, J. G. Neilan, D. L. Rock

Research output: Contribution to journalArticlepeer-review

Abstract

The African swine fever virus (ASFV) genome contains a gene, 9GL, with similarity to yeast ERV1 and ALR genes. ERV1 has been shown to function in oxidative phosphorylation and in cell growth, while ALR has hepatotrophic activity. 9GL encodes a protein of 119 amino acids and was highly conserved at both nucleotide and amino acid levels among all ASFV field isolates examined. Monospecific rabbit polyclonal antibody produced to a glutathione S-transferase-9GL fusion protein specifically immunoprecipitated a 14-kDa protein from macrophage cell cultures infected with the ASFV isolate Malawi Lil-20/1 (MAL). Time course analysis and viral DNA synthesis inhibitor experiments indicated that p14 was a late viral protein. A 9GL gene deletion mutant of MAL (Δ9GL), exhibited a growth defect in macrophages of approximately 2 log10 units and had a small-plaque phenotype compared to either a revertant (9GL-R) or the parental virus. 9GL affected normal virion maturation; virions containing acentric nucleoid structures comprised 90 to 99% of all virions observed in Δ9GL-infected macrophages. The Δ9GL virus was markedly attenuated in swine. In contrast to 9GL-R infection, where mortality was 100%, all Δ9GL-infected animals survived infection. With the exception of a transient fever response in some animals, Δ9GL-infected animals remained clinically normal and exhibited significant 100- to 10,000- fold reductions in viremia titers. All pigs previously infected with Δ9GL survived infection when subsequently challenged with a lethal dose of virulent parental MAL. Thus, ASFV 9GL gene deletion mutants may prove useful as live-attenuated ASF vaccines.

Original languageEnglish (US)
Pages (from-to)1275-1285
Number of pages11
JournalJournal of virology
Volume74
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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