Anti-human immunodeficiency virus activity of tau interferon in human macrophages: involvement of cellular factors and beta-chemokines.
Tau interferon (IFN-tau) is a noncytotoxic type I IFN responsible for maternal recognition of the fetus in ruminants. IFN-tau inhibits human immunodeficiency virus (HIV) replication more strongly than human IFN-alpha, particularly in human monocyte-derived macrophages. In this study performed in human macrophages, IFN-tau efficiently inhibited the early steps of the biological cycle of HIV, decreasing intracellular HIV RNA and inhibiting the initiation of the reverse transcription of viral RNA into proviral DNA. Two mechanisms induced by IFN-tau treatment in macrophages may account for this inhibition: (i) the synthesis of the cellular antiviral factors such as 2',5'-oligoadenylate synthetase/RNase L and MxA protein and (ii) an increased production of MIP-1alpha, MIP-1beta, and RANTES, which are natural ligands of CCR5, the principal coreceptor of HIV on macrophages. Our results suggest that IFN-tau induces the same antiviral pathways in macrophages as other type I IFNs but without associated toxicity.
Rogez
Christine
C
Service de Neurovirologie. SPI-BIO, c/o Service de Neurovirologie, CEA, CRSSA, Université Paris Sud, EPHE, IPSC, Fontenay-aux-Roses, France.
Martin
Marc
M
Dereuddre-Bosquet
Nathalie
N
Martal
Jacques
J
Dormont
Dominique
D
Clayette
Pascal
P
D019742:Chemokines, CC / Q000502:physiology*; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D011257:Pregnancy Proteins / Q000494:pharmacology*; D012367:RNA, Viral / Q000097:blood; D014158:Transcription, Genetic; D014779:Virus Replication / Q000187:drug effects*
D019742:Chemokines, CC; D007370:Interferon Type I; D011257:Pregnancy Proteins; D012367:RNA, Viral; C020947:interferon tau