Abstract
HIV-1 infection of myeloid cells is associated with the induction of an IFN response. How HIV-1 manipulates and subverts the IFN response is of key interest for the design of therapeutics to improve immune function and mitigate immune dysregulation in people living with HIV. HIV-1 accessory genes function to improve viral fitness by altering host pathways in ways that enable transmission to occur without interference from the immune response. We previously described changes in transcriptomes from HIV-1 infected and from IFN-stimulated macrophages and noted that transcription of IFN-regulated genes and genes related to cell cycle processes were upregulated during HIV-1 infection. In the present study, we sought to define the roles of individual viral accessory genes in upregulation of IFN-regulated and cell cycle-related genes using RNA sequencing. We observed that Vif induces a set of genes involved in mitotic processes and that these genes are potently downregulated upon stimulation with type-I and -II IFNs. Vpr also upregulated cell cycle-related genes and was largely responsible for inducing an attenuated IFN response. We note that the induced IFN response most closely resembled a type-III IFN response. Vpu and Nef-regulated smaller sets of genes whose transcriptomic signatures upon infection related to cytokine and chemokine processes. This work provides more insight regarding processes that are manipulated by HIV-1 accessory proteins at the transcriptional level.
Highlights
Human immunodeficiency type 1 (HIV-1) targets several key immune cells which respond to viral insult through the generation of an innate immune response [1]
We sought to better understand how changes in the macrophage transcriptome induced by HIV-1 infection compare with changes after stimulation with interferons
HIV-1-upregulated genes were present among genes upregulated by all four IFNs tested, with IFN-λ stimulation sharing the largest number of common upregulated genes (Figure 1b)
Summary
Human immunodeficiency type 1 (HIV-1) targets several key immune cells which respond to viral insult through the generation of an innate immune response [1]. This response, driven by detection of pathogen-associated molecular patterns (PAMPs), leads to the formation of an antiviral state [1]. While there has been a significant effort to understand the role of type-I IFNs in this process, less is understood about the landscape of additional IFN subtypes (i.e., II and III), their impact on HIV-1 infection, and whether the innate immune response in macrophages more closely resembles their IRG signatures [4,5,6]. Several studies have failed to detect type-I IFN production itself at the protein or mRNA level during in vitro infection of MDM with HIV-1, despite the induction of numerous IRGs [2,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
