Ovine lentivirus-infected macrophages mediate productive infection in cell types that are not susceptible to infection with cell-free virus.

Abstract

Ovine lentiviruses and caprine arthritis-encephalitis virus (CAEV) are prototypic lentiviruses that replicate predominantly in macrophages of infected animals. In situ hybridization of pathologically affected tissues from diseased animals has shown that viral RNA exists in permissive macrophages as well as in non-macrophage cell types that do not support productive virus replication. These findings raise questions about the cellular tropism of these viruses in vivo and how this may relate to their pathogenesis and the establishment of persistent infections. In this study, the susceptibility of macrophages and fibro-epithelial cells derived from goat synovial membrane (GSM) to infection by 14 North American ovine lentivirus strains was examined. All 14 strains were macrophagetropic, as indicated by expression of viral proteins and by fusion and development of syncytial cytopathic effects following co-culture of infected macrophages with GSM cells. In contrast, neither viral DNA nor viral proteins was detected in GSM cells inoculated with cell-free virus from nine of the 14 strains. Specific virus proteins were immunoprecipitated from restrictive GSM cells following culture with infected macrophages and serial passage of GSM cells to remove the macrophages. The lack of infection of GSM cells by cell-free virus from some ovine lentivirus field strains was circumvented by cell-associated virus infection from infected macrophages to GSM cells following cell-to-cell contact. This strategy could be one of the mechanisms involved in the escape from immune surveillance and establishment of persistent infection in infected animals.

Lack of Functional Receptors Is the Only Barrier That Prevents Caprine Arthritis-Encephalitis Virus from Infecting Human Cells

“…These data clearly suggest that CAEV might be considered as potentially able to cross the species barrier to human cells by a single acquisition of novel receptor specificity or by the cooperation of a helper virus. We also cannot exclude the possibility of infection of human cells following cell-to-cell contact with infected goat cells as we recently described for small-ruminant cells resistant to infection by ovine field isolates (34).…”

“…We used the human ␤-actin gene as an internal control for the integrity of the DNA lysates. After the second round of amplification using the actin primers, a fragment of 390 bp was expected as previously described (34).…”

“…RNA was reverse transcribed using Moloney murine leukemia virus reverse transcriptase and random hexamer primers as reported previously (23). PCR analysis was performed using the Gag primers GEX5 and GEX3 previously described (34).…”

“…PCR analysis was performed on cell lysates by using Gag and actin primers as previously described (34). To increase the sensitivity of DNA amplification, two rounds of PCR were performed.…”

Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding

“…However, it is still not known how to identify predominant forms of infectious virions for OvLV. There are open questions about transmission through cell-associated virus versus free viral particles [212,213,214]. While recent advances have provided important clues [215], there is still no way to reliably measure shedding of OvLV in ways meaningful for natural transmission.…”