Myeloid cells play numerous roles in HIV-1 pathogenesis serving as a vehicle for viral spread and as a viral reservoir. Yet, cells of this lineage generally resist HIV-1 infection when compared to cells of other lineages, a phenomenon particularly acute during the early phases of infection. Here, we explore the role of APOBEC3A on these steps. APOBEC3A is a member of the APOBEC3 family that is highly expressed in myeloid cells, but so far lacks a known antiviral effect against retroviruses. Using ectopic expression of APOBEC3A in established cell lines and specific silencing in primary macrophages and dendritic cells, we demonstrate that the pool of APOBEC3A in target cells inhibits the early phases of HIV-1 infection and the spread of replication-competent R5-tropic HIV-1, specifically in cells of myeloid origins. In these cells, APOBEC3A affects the amount of vDNA synthesized over the course of infection. The susceptibility to the antiviral effect of APOBEC3A is conserved among primate lentiviruses, although the viral protein Vpx coded by members of the SIV_SM/HIV-2 lineage provides partial protection from APOBEC3A during infection. Our results indicate that APOBEC3A is a previously unrecognized antiviral factor that targets primate lentiviruses specifically in myeloid cells and that acts during the early phases of infection directly in target cells. The findings presented here open up new venues on the role of APOBEC3A during HIV infection and pathogenesis, on the role of the cellular context in the regulation of the antiviral activities of members of the APOBEC3 family and more generally on the natural functions of APOBEC3A. Macrophages and dendritic cells represent important targets for HIV-1 and the understanding of the complex relationship established between these cells and the virus is of the outmost importance. Here, we show that APOBEC3A, the least known member of the APOBEC3 family of cytidine deaminases, restricts HIV-1 specifically in these cells. The antiviral effect of APOBEC3A is exerted at viral DNA accumulation during de novo infection through a mechanism that may involve deamination. For the first time, our results indicate that APOBEC3A, rather than being devoid of inhibitory activity against HIV-1, plays an important role in blocking not only HIV-1, but more generally primate lentiviruses. This antiviral effect is specific to myeloid cells in which this factor is naturally expressed. Among the viral proteins capable of opposing APOBEC3A, we have found that Vpx, a protein coded by members of the SIV_SM/HIV-2 lineage provides a partial protection against this factor by inducing its degradation. Overall, these results shed new light on the regulation of members of the APOBEC3 family in primary cells and open up new venues on the role that APOBEC3A, a restriction factor specifically expressed in myeloid cells, may play during viral pathogenesis.

Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of antiviral inhibition indicates that the pool of IFITM proteins present in target cells blocks incoming viral particles in endosomal vesicles where they are subsequently degraded. In this study, we describe an additional mechanism through which IFITMs block HIV-1. In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into viral particles. Expression of IFITMs during virion assembly leads to the production of virion particles of decreased infectivity that are mostly affected during entry in target cells. This mechanism of inhibition is exerted against different retroviruses and does not seem to be dependent on the type of Envelope present on retroviral particles. The results described here identify a novel mechanism through which IFITMs affect HIV-1 infectivity during the late phases of the viral life cycle. Put in the context of data obtained by other laboratories, these results indicate that IFITMs can target HIV at two distinct moments of its life cycle, in target cells as well as in virus-producing cells. These results raise the possibility that IFITMs could similarly affect distinct steps of the life cycle of a number of other viruses.

Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them.

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Radiogenomics aims at investigating the relationship between imaging radiomic features and gene expression alterations. This study addressed the potential prognostic complementary value of contrast enhanced computed tomography (CE-CT) radiomic features and gene expression data in primary colorectal cancers (CRC). Sixty-four patients underwent CT scans and radiomic features were extracted from the delineated tumor volume. Gene expression analysis of a small set of genes, previously identified as relevant for CRC, was conducted on surgical samples from the same tumors. The relationships between radiomic and gene expression data was assessed using the Kruskal–Wallis test. Multiple testing was not performed, as this was a pilot study. Cox regression was used to identify variables related to overall survival (OS) and progression free survival (PFS). ABCC2 gene expression was correlated with N (p = 0.016) and M stages (p = 0.022). Expression changes of ABCC2, CD166, CDKNV1 and INHBB genes exhibited significant correlations with some radiomic features. OS was associated with Ratio 3D Surface/volume (p = 0.022) and ALDH1A1 expression (p = 0.042), whereas clinical stage (p = 0.004), ABCC2 expression (p = 0.035), and Entropy_{GLCM_E} (p = 0.0031), were prognostic factors for PFS. Combining CE-CT radiomics with gene expression analysis and histopathological examination of primary CRC could provide higher prognostic stratification power, leading to improved patient management.