| First Author | Browne EP | Year | 2015 |
| Journal | J Virol | Volume | 89 |
| Issue | 1 | Pages | 155-64 |
| PubMed ID | 25320301 | Mgi Jnum | J:221393 |
| Mgi Id | MGI:5639004 | Doi | 10.1128/JVI.02314-14 |
| Citation | Browne EP (2015) An interleukin-1 beta-encoding retrovirus exhibits enhanced replication in vivo. J Virol 89(1):155-64 |
| abstractText | Interleukin-1 beta (IL-1beta) is an inflammatory cytokine that is secreted in response to inflammasome activation by innate microbe-sensing pathways. Although some retroviruses can trigger IL-1beta secretion through the DNA-sensing molecule IFI16, the effect of IL-1beta on the course of infection is unknown. To test whether IL-1beta secretion affects retroviral replication in vivo, I constructed a novel murine leukemia virus strain (FMLV-IL-1beta) that encodes the mature form of IL-1beta. This virus replicated with kinetics similar to that of wild-type virus in tissue culture but caused a dramatically more aggressive infection of both C57BL/6 and BALB/c mice. By 7 days postinfection (PI), mice infected with FMLV-IL-1beta exhibited splenomegaly and viral loads 300-fold higher than those in mice infected with wild-type FMLV. Furthermore, the enlarged spleens of FMLV-IL-1beta-infected mice correlated with a large expansion of Gr-1(+) CD11b(+) myeloid-derived suppressor cells, as well as elevated levels of immune activation. Although FMLV-IL-1beta infection was controlled by C57BL/6 mice by 14 days p.i., FMLV-IL-1beta was able to establish a significant persistent infection and immune activation in BALB/c mice. These results demonstrate that IL-1beta secretion is a powerful positive regulator of retroviral infection and that FMLV-IL-1beta represents a new model of proinflammatory retroviral infection. IMPORTANCE: Interleukin-1 beta (IL-1beta) is an inflammatory cytokine released in response to activation of innate pathogen-sensing pathways during microbial infection. To examine the potential impact of IL-1beta on retroviral replication in vivo, I constructed a novel mouse retrovirus strain (FMLV-IL-1beta) that encodes IL-1beta and promotes abundant IL-1beta secretion from infected cells. This virus replicates with normal kinetics in cultured cells but displays a dramatically enhanced ability to replicate in mice and caused persistent infection and immune activation in the BALB/c strain of mice. These results establish IL-1beta as a positive regulator of retroviral replication and suggest that targeting this pathway may have therapeutic benefits in infections with proinflammatory retroviruses. This virus can also be used to further study the impact of inflammatory pathways on retroviral infection. |
