Comparison of Antiviral Activity of Lambda-Interferons Against HIV Replication in Macrophages

Abstract

Lambda-interferons (IFN-ls) have been demonstrated as having the ability to inhibit HIV replication in macrophages. However, specific differences in signaling transduction and anti-HIV activity in macrophages between different IFN-ls are unclear. Here, we showed that although all 3 members of (IFN-l1, l2, and l3) IFN-l family induced the expression of a number of genes of janus kinase/signal transducers and activators of transcription ( JAK/STAT) signaling pathway in monocyte-derived macrophages, IFN-l1 or IFN-l3 induced higher levels of antiviral IFN-stimulated genes (ISGs) expression than did IFN-l2. In addition, IFN-l1 or IFN-l3 induced higher levels of several pattern recognition receptors (PPRs) than did IFN-l2. Incubation of IFN-ls with HIV-infected macrophages showed that IFN-l1 or IFN-l3 is more potent in anti-HIV activity than IFN-l2. We also showed that IFN-l treatment before HIV infection was more potent in HIV inhibition than that after HIV infection. Further investigations showed that the inductions of ISGs and PPRs expression by IFN-ls were largely compromised by HIV infection. These findings provide further experimental evidence that IFN-ls have therapeutic potential in treatment of HIV infection.

IFN‐λ4 inhibits HIV infection of macrophages through signalling of IFN‐λR1/IL‐10R2 receptor complex

“…HIV RT activities were compared between the group treated with IFN-λ4 alone and the other groups. *P < 0.05, **P < 0.01 inhibit HIV replication, [8][9][10] it remains to be determined whether IFN-λ4 possesses the anti-HIV function. In the present study, we treated macrophages with different doses of IFN-λ4 before, simultaneous or after HIV infection.…”

“…7 Studies from different laboratories have documented that IFN-λ1, 2 and 3 have the ability to inhibit HIV replication. [8][9][10] It is unknown, however, whether IFN-λ4 has anti-HIV activity. In the present study, we investigated the antiviral effect of IFN-λ4 on HIV infection of macrophages, a major target of HIV infection and potential longterm HIV reservoir.…”

Interferons and beyond: Induction of antiretroviral restriction factors

“…Moreover, IFNλ also enhanced APOBEC3G and APOBEC3F expression, although it remained unclear whether this upmodulation contributed to the observed antiretroviral effect and whether it was a direct effect of IFNλ, or a side effect of type I IFN upregulation . A study comparing the inhibitory effect of different members of the IFNλ family in monocyte‐derived macrophages (MDM) revealed, that IFNλ1, IFNλ3, and to a lesser extent IFNλ2 induced expression of several ISGs . The induced ISGs included potential HIV‐1 inhibitors such as 2’‐5’‐oligoadenylat synthetase (OAS)1 or ISG15, which degrade viral RNAs or inhibit viral particle assembly, respectively.…”

“…The induced ISGs included potential HIV‐1 inhibitors such as 2’‐5’‐oligoadenylat synthetase (OAS)1 or ISG15, which degrade viral RNAs or inhibit viral particle assembly, respectively. In line with enhanced ISG expression, IFNλ1 and IFNλ3 inhibited HIV‐1 more potently than IFNλ2 . The antiviral effect of type III IFNs seems not to be limited to macrophages, since also pre‐treatment of primary CD4+ T cells with IFNλ1 and IFNλ2 suppressed HIV‐1 integration and post‐transcriptional events …”

“…Type III IFNs, also called IFN , are the most recently discovered class of the three types of IFN, 60 and to a lesser extent IFN 2 induced expression of several ISGs. 66 The induced ISGs included potential HIV-1 inhibitors such as 2'-5'oligoadenylat synthetase (OAS)1 or ISG15, which degrade viral RNAs or inhibit viral particle assembly, respectively. In line with enhanced ISG expression, IFN 1 and IFN 3 inhibited HIV-1 more potently than IFN 2.…”