DELETION OF A CD2-LIKE GENE, 8-DR, FROM AFRICAN SWINE FEVER VIRUS AFFECTS VIRAL-INFECTION IN DOMESTIC SWINE

An African swine fever virus (ASFV) gene with similarity to the T-lymp hocyte surface antigen CD2 has been found in the pathogenic African is olate Malawi Lil-20/1 (open reading frame [ORF] 8-DR) and a cell cultu re-adapted European virus, BA71V (ORF EP402R) and has been shown to be responsible for the hemadsorption phenomenon observed for ASFV-infect ed cells. The structural and functional similarities of the ASFV gene product to CD2, a cellular protein involved in cell-cell adhesion and T-cell-mediated immune responses, suggested a possible role for this g ene in tissue tropism and/or immune evasion in the swine host, In this study, we constructed an ASFV 8-DR gene deletion mutant (Delta 8-DR) and its revertant (8-DR.R) from the Malawi Lil-20/1 isolate to examine gene function in vivo. In vitro, rig-DR, 8-DR.R, and the parental vir us exhibited indistinguishable growth characteristics on primary porci ne macrophage cell cultures. In vivo, 8-DR had no obvious effect on vi ral virulence in domestic pigs; disease onset, disease course, and mor tality were similar for the mutant Delta 8-DR its revertant 8-DR.R and the parental virus. Altered viral infection was, however, observed fo r pigs infected with Delta 8-DR. A delay in spread to and/or replicati on of Delta 8-DR in the draining lymph node, a delay in generalization of infection, and a 100- to 1,000-fold reduction in virus titers in l ymphoid tissue and bone marrow were observed. Onset of viremia for Del ta 8-DR-infected animals was significantly delayed (by 2 to 5 days), a nd mean viremia titers were reduced approximately 10,000-fold at 5 day s postinfection and 30- to 100-fold at later times; moreover, unlike i n 8-DR.R-infected animals, the viremia was no longer predominantly ery throcyte associated but rather was equally distributed among erythrocy te, leukocyte, and plasma fractions. Mitogen-dependent lymphocyte prol iferation of swine peripheral blood mononuclear cells in vitro aas red uced by 90 to 95% following infection with 8-DR.R but remained unalter ed following infection with Delta 8-DR, suggesting that 8-DR has immun osuppressive activity in vitro. Together, these results suggest an imm unosuppressive role far 8-DR in the swine host which facilitates early events in viral infection. This may be of most significance for ASFV infection of its highly adapted natural host, the warthog.