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Article
| Open Access
Antiretroviral APOBEC3 cytidine deaminases alter HIV-1 provirus integration site profiles
Antiretroviral APOBEC3 may contribute to HIV-1 latency. In this study, Ajoge and Renner et al. identify a previously undescribed function of human APOBEC3 proteins in redirecting integrations of HIV-1 DNA into more transcriptionally inactive regions of the genome.
- Hannah O. Ajoge
- , Tyler M. Renner
- & Stephen D. Barr
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Article
| Open Access
Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G
Interaction between APOBEC3G and RNA is critical for its antiviral function. Here, the authors report four co-crystal structures of rhesus macaque APOBEC3G and RNA, demonstrating unpaired AA and GA dinucleotide motifs are preferentially recognized.
- Hanjing Yang
- , Kyumin Kim
- & Xiaojiang S. Chen
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Article
| Open Access
TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV
The human silencing hub (HUSH) complex, which includes TASOR, deposits repressive marks on HIV proviruses, resulting in gene repression. Here, Matkovic et al. show that TASOR interacts with RNA Polymerase II, predominantly under its elongating state, and RNA degradation proteins to repress HIV provirus expression.
- Roy Matkovic
- , Marina Morel
- & Florence Margottin-Goguet
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Article
| Open Access
SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells
SAMHD1 is a cellular dNTPase proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting dNTP substrate supply; its anti-viral but not dNTPase function is downregulated by phosphorylation of T592. Here, Martinat et al. describe an additional SUMOylation at residue K595, which promotes the dNTPase-independent restriction activity.
- Charlotte Martinat
- , Arthur Cormier
- & Alessia Zamborlini
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Article
| Open Access
Vpr counteracts the restriction of LAPTM5 to promote HIV-1 infection in macrophages
Here, using proteomics and cell-based assays, the authors show that HIV accessory protein Vpr mediates the degradation of host lysosomal-associated transmembrane protein 5 (LAPTM5) in monocyte-derived macrophages (MDM) to enhance infection in macrophages.
- Li Zhao
- , Shumei Wang
- & Guoxin Liang
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Article
| Open Access
A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry
The SARS-CoV-2 spike protein contains a multi-basic cleavage site. Here, the authors show how this multi-basic cleavage site affects entry of SARS-CoV-2 into cells and transmission in the hamster model and identify host factors affecting entry of SARS-CoV-2 in a genome-wide CRISPR screen.
- Yunkai Zhu
- , Fei Feng
- & Rong Zhang
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Article
| Open Access
Identification of interferon-stimulated genes that attenuate Ebola virus infection
Here, Kuroda et al. screen a library of nearly 400 interferon-stimulated genes (ISGs) and identify several ISGs that inhibit Ebola virus entry, viral transcription/replication, or virion formation. The study provides insights into interactions between Ebola and the host cells.
- Makoto Kuroda
- , Peter J. Halfmann
- & Yoshihiro Kawaoka
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Article
| Open Access
Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses
Cytosolic mitochondrial DNA (mtDNA) plays a role in innate antiviral immunity but how this is triggered during infection remains unclear. Here, the authors provide evidence that the Influenza virus protein M2 stimulates translocation of mtDNA into the cytosol in a MAVS-dependent manner.
- Miyu Moriyama
- , Takumi Koshiba
- & Takeshi Ichinohe
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Article
| Open Access
PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation
The accessory lentiviral protein X (Vpx) of the SIVsmm/mac and HIV-2 lineage targets the host-restriction factor SAMHD1 for proteasomal degradation. Here, the authors show that host PIM kinase-mediated phosphorylation of Vpx stabilizes its interaction with SAMHD1, suggesting PIM as potential antiviral targets.
- Kei Miyakawa
- , Satoko Matsunaga
- & Akihide Ryo
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Article
| Open Access
Dephosphorylation of the HIV-1 restriction factor SAMHD1 is mediated by PP2A-B55α holoenzymes during mitotic exit
SAMHD1 is a critical restriction factor for HIV-1 and its antiviral activity is regulated by T592 phosphorylation. Here, Schott et al. show that the phosphatase PP2A-B55α dephosphorylates SAMHD1 during mitotic exit, rendering it antivirally active in G1 phase of primary CD4+ T cells.
- Kerstin Schott
- , Nina V. Fuchs
- & Renate König
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Article
| Open Access
MxB is an interferon-induced restriction factor of human herpesviruses
MxB is an interferon-induced GTPase that inhibits HIV replication. Here, Crameri et al. show that MxB restricts replication of herpesviruses by inhibiting delivery of incoming viral DNA into the nucleus, and this antiviral activity depends on MxB’s GTPase activity.
- Michel Crameri
- , Michael Bauer
- & Jovan Pavlovic
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Article
| Open Access
APOBEC3H structure reveals an unusual mechanism of interaction with duplex RNA
The APOBEC3 family cytidine deaminases with antiviral activity are proteins that catalyze the deamination of newly reverse-transcribed viral DNA. Here the authors present the crystal structure of full-length pig-tailed macaque APOBEC3H with bound RNA, which reveals how the APOBEC3H dimer binds around a short RNA duplex.
- Jennifer A. Bohn
- , Keyur Thummar
- & Janet L. Smith
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Article
| Open Access
Dimerization regulates both deaminase-dependent and deaminase-independent HIV-1 restriction by APOBEC3G
APOBEC3G inhibits HIV-1 viral replication via catalytic and non-catalytic processes. Here the authors show that APOBEC3G binds single-stranded DNA as an active deaminase monomer, subsequently forming catalytic-inactive dimers that block reverse transcriptase-mediated DNA synthesis.
- Michael Morse
- , Ran Huo
- & Mark C. Williams
PRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex