IFI44 is an interferon-alfa inducible protein, and is associated with infection of several viruses. However, IFI44 elicits minimal antiviral effects on these viruses, and its exact role is still unknown. Here we show that IFI44 inhibits HIV-1 replication in vitro. Through depletion of endogenous IFI44 or overexpression of IFI44 we confirm that IFI44 suppresses HIV-1 LTR promoter activity and affects viral transcription. Furthermore, we find that IFI44 localizes to nuclei and binds to the HIV-1 LTR promoter in HIV-1 infected cells. Removing suppression of HIV-1 transcription benefits reactivation of HIV-1 proviruses for purging latent reservoirs. We demonstrate that depletion of endogenous IFI44 in J-LAT cells induces reactivation of latent HIV-1. Based on these results, we propose a model in which IFI44 is recruited to the HIV-1 LTR, which may suppress viral transcription and prevent reactivation of latent HIV-1. Our study suggests a previously unrecognized anti-HIV phenomenon for interferon-stimulated proteins.

Background: FACT proteins SUPT16H and SSRP1 are identified as host factors that restrict HIV-1 replication. Results: Biochemical and genetic evidences that SUPT16H and SSRP1 affect HIV-1/HTLV-1 transcription and latency are provided. Conclusion: SUPT16H and SSRP1 suppress transcription of HIV-1/HTLV-1, and their presence may promote HIV-1 latency. Significance: Identification of host factors necessary for HIV-1 latency is critical, which may benefit the development of novel HIV-1 latency-reversing agents.

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ObjectiveWe have previously described the generation of coxsackievirus and adenovirus receptor (α CAR)‐targeted vector, and shown that intramuscular delivery in mouse leg muscles resulted in specific retrograde transduction of lumbar‐motor neurons (MNs). Here, we utilized the α CAR‐targeted vector to investigate the in vivo neuroprotective effects of lentivirally expressed IGF‐1 for inducing neuronal survival and ameliorating the neuropathology and behavioral phenotypes of the SOD1G93A mouse model of ALS.MethodsWe produced cell factories of IGF‐1 expressing lentiviral vectors (LVs) bearing α CAR or Vesicular Stomatitis Virus glycoprotein (VSV‐G) on their surface so as to compare neuroprotection from MN transduced versus muscle transduced cells. We performed intramuscular delivery of either α CAR IGF‐1 or VSVG IGF‐1 LVs into key muscles of SOD1G93A mice prior to disease onset at day 28. Motor performance, coordination and gait analysis were assessed weekly.ResultsWe observed substantial therapeutic efficacy only with the α CAR IGF‐1 LV pretreatment with up to 50% extension of survival compared to controls. α CAR IGF‐1 LV‐treated animals retained muscle tone and had better motor performance during their prolonged survival. Histological analysis of spinal cord samples at end‐stage further confirmed that α CAR IGF‐1 LV treatment delays disease onset by increasing MN survival compared with age‐matched controls. Intrastriatal injection of α CAR eGFP LV in rats leads to transduction of neurons and glia locally and neurons in olfactory bulb distally.InterpretationOur data are indicative of the efficacy of the α CAR IGF‐1 LV in this model and support its candidacy for early noninvasive neuroprotective therapy in ALS.