TY - JOUR
T1 - Regulation of interferon-α-inducible cellular genes in human immunodeficiency virus-infected monocytes
AU - Baca, L. M.
AU - Genis, P.
AU - Kalvakolanu, D.
AU - Sen, G.
AU - Meltzer, M. S.
AU - Zhou, A.
AU - Silverman, R.
AU - Gendelman, H. E.
PY - 1994
Y1 - 1994
N2 - Cellular mechanisms that control susceptibility to opportunistic infection in human immunodeficiency virus (HIV)-infected individuals remain poorly understood. HIV may induce certain cellular genes that restrict HIV replication and protect cells against other superinfecting viral pathogens. Indeed, HIV-infected monocytes resist infection by vesicular stomatitis virus (VSV). HIV-induced VSV interference in monocytes increases with time after HIV infection. Such interference was evident 6 h after HIV infection and reached maximal levels at 14 days. Monocytotropic but not T cell-tropic HIV strains elicited these effects, signaling a requirement for viral entry and/or replication. Viral interference was independent of interferon (IFN) and was unaffected by addition of neutralizing IFN-α and -β antibodies. The well-described IFN-α-inducible antiviral pathways were examined to determine their relationship to the cellular mechanism(s) underlying VSV interference. HIV and IFN-α both induced the expression of 2-5A synthetase and Mx gene. In contrast, the guanylate-binding protein (GBP), 6-16, and 9-27 cellular genes were up-regulated by IFN-α but not HIV. MxA was detected in HIV-infected monocytes but not in uninfected monocytes. The association between Mx expression and resistance to VSV, coupled with previously described anti-VSV activities by human MxA, suggested that Mx may be an effector molecule for the HIV-induced anti-VSV activities. These results, taken together, suggest that HIV can induce antiviral cellular gene expression, independent of IFN.
AB - Cellular mechanisms that control susceptibility to opportunistic infection in human immunodeficiency virus (HIV)-infected individuals remain poorly understood. HIV may induce certain cellular genes that restrict HIV replication and protect cells against other superinfecting viral pathogens. Indeed, HIV-infected monocytes resist infection by vesicular stomatitis virus (VSV). HIV-induced VSV interference in monocytes increases with time after HIV infection. Such interference was evident 6 h after HIV infection and reached maximal levels at 14 days. Monocytotropic but not T cell-tropic HIV strains elicited these effects, signaling a requirement for viral entry and/or replication. Viral interference was independent of interferon (IFN) and was unaffected by addition of neutralizing IFN-α and -β antibodies. The well-described IFN-α-inducible antiviral pathways were examined to determine their relationship to the cellular mechanism(s) underlying VSV interference. HIV and IFN-α both induced the expression of 2-5A synthetase and Mx gene. In contrast, the guanylate-binding protein (GBP), 6-16, and 9-27 cellular genes were up-regulated by IFN-α but not HIV. MxA was detected in HIV-infected monocytes but not in uninfected monocytes. The association between Mx expression and resistance to VSV, coupled with previously described anti-VSV activities by human MxA, suggested that Mx may be an effector molecule for the HIV-induced anti-VSV activities. These results, taken together, suggest that HIV can induce antiviral cellular gene expression, independent of IFN.
KW - HIV-infected monocytes
KW - INF-α-inducible genes
KW - vesicular stomatitis virus
UR - http://www.scopus.com/inward/record.url?scp=0028220493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028220493&partnerID=8YFLogxK
U2 - 10.1002/jlb.55.3.299
DO - 10.1002/jlb.55.3.299
M3 - Article
C2 - 7509841
AN - SCOPUS:0028220493
SN - 0741-5400
VL - 55
SP - 299
EP - 309
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -