HIV-1 is a poor inducer of innate immune responses

Abstract

Effective host immune responses against viral infection rely on the detection of the virus, activation of downstream signaling pathways, and the secretion of interferons (IFNs) and other cytokines. Many viruses can potently stimulate these responses, whereas the immune response against human immunodeficiency virus type 1 (HIV-1) remains relatively less well characterized. Here we show that HIV-1 infection with reporter viruses does not activate sensing pathways in cell lines and primary cells that are otherwise responsive to foreign nucleic acids. After entry into cells, reverse transcription and reporter expression occur without the virus ever being detected by cellular sensors or stimulating an interferon response. Using multiple methods, including the use of reporter cell lines for type I IFN and NF-κB pathway activation, quantifying mRNA levels for IFN-stimulated genes (ISGs), and assaying for markers of innate immune activation, we show that single-round pseudotyped HIV-1-based reporter viruses fail to induce innate immune responses. IMPORTANCE Human immunodeficiency virus type 1 (HIV-1) continues to be a major burden to human health worldwide. How infected cells recognize and respond to HIV-1 infection is important in order to better understand the biology of the virus and the cellular pathways activated upon infection and to identify potential targets that interfere with viral replication. In this study, we investigated innate immune responses of different cell types following infection with single-cycle (replicationdefective) HIV-1 reporter virus. We report that infection with a commonly used HIV-1 strain (lacking the env, nef, and vpr genes) does not measurably activate cellular defense mechanisms and that the virus is able to avoid recognition by cellular sensors.