Out of the 69 FIV induced genes (Additional file
1: Table S1); several genes have already been described to be affected also by infection with other viruses, in particular HIV. OASL, the most significantly regulated gene upon FIV infection (up-regulated 3.4-fold; Table
2) is known as an antiviral protein, induced by a variety of viruses, such as the influenza A and hepatitis C virus[
15,
16]. Other examples include DHX58 and DDX58 (up 2.6- and 2.8-folds), belonging to the group of RNA helicases. These enzymes are involved in many processes of the cellular RNA metabolism including the sensing of viral RNAs and the mediation of antiviral immune responses[
17]. ACHE (up 2.6-fold) encodes for an enzyme necessary for the termination of neuro-transmitted signals. Furthermore, the plasma secretion of this protein is accomplished via exosome-like vesicles that are also used by HIV for the release of viral Nef proteins. Thus, HIV increases ACHE expression and vesicle production in order to enhance the export of its own proteins[
18]. We detected TGM2 to be highly up-regulated (up 5.4-fold) after FIV infection, similar to previous findings for HIV[
19]. This multifunctional protein is involved in several cellular processes including apoptosis. The induction of TGM2 might be an antiviral mechanism of the host cells in order to trigger apoptosis and interfere with virus replication[
20]. HMGN2 (down 2.1-fold) is presumed to be involved in HIV replication due to interactions with the viral integrase[
21]. CDKN1A (other names: p21/waf1; up 2.1-fold) encodes a cyclin-dependent kinase inhibitor that functions as a regulator of cell cycle progression, especially in the promotion of cell cycle arrest. HIV affects the function of the encoded protein and thus, influences cell cycle progression[
22]. The induction of cell cycle arrest might benefit viruses because of the resulting suppression of immune responses and the generation of an optimized cellular environment for viral reproduction[
23]. In contrast, the increase of ZFP36 (tristetraprolin; up 2.0-fold) might be an antiviral response of the host cell. ZFP36, due to its zinc finger motifs, is able to interact with specific AU-rich regions of HIV RNAs and consequently targets them for rapid degradation[
24]. Together with other cellular defense mechanisms, this process may represent an additional antiviral barrier that aims to block virus replication at the transcription level. Similar functions, as a transcriptional repressor of HIV have also been described for BCL6 (up 2.1-fold)[
25]. Other examples of genes affected by FIV that have previously been associated with HIV pathogenesis include CSF1, IFI44, HSPE1 and CXCL11. The protein encoded by CSF1 (up 2.0-fold) is a secreted cytokine that controls the production, differentiation and function of macrophages. The induction of this pro-survival cytokine by HIV facilitates protection infected cells from apoptosis[
26]. IFI44 (MTAp44; up 2.6-fold) is inducible by interferons (IFNs) which are released by cells in response to the presence of viruses, bacteria and parasites. IFNs trigger the early antiviral defense of the immune system that aims to eradicate the pathogens. IFI44 is frequently upregulated in virus infected cells generating an antiproliferative state, impeding viral replication[
27,
28]. HSPE1 (up 3.0-fold) encodes a major heat shock protein. These stress proteins are expressed in response to a broad range of stimuli such as heat and microbial infections. Additionally, interactions with HIV suggest functions in the regulation of viral gene expression and replication[
29]. Another IFN induced gene is CXCL11 (up 3.1-fold) which functions as a chemokine and is the dominant ligand for the CXC receptor-3 on immune cells. Its release initiates a chemotactic response in activated T-cells recruiting them to lymphoid organs. In the case of lentiviral infections, the migration of additional cells to infected lymph nodes increases the numbers of potential target cells and thus, contributes to the spread of infection[
30].
Several of the DEGs identified in this study are known to interact with HIV accessory proteins that are missing in FIV. The HIV Tat protein functions as an activator of viral RNA transcription and is responsible for the induction of several cellular genes, such as CDKN1A[
31], BCL6[
32], IFI44[
27], C1QTNF5, EEFCC1[
33] and COX4I1[
34]. For CDKN1A, additional interactions have been described with HIV Vpr[
35]. As we observed expression changes for all these genes also in this study, similar mechanisms can be assumed for FIV. Here, other viral genes might adopt the particular functions attributed to HIV Tat and Vpr.