Huntingtin-interacting Protein 1 Promotes Vpr-induced G2 Arrest and HIV-1 Infection in Macrophages
Background: Human immunodeficiency virus type 1 (HIV-1) modulates the host cell cycle. The HIV-1 accessory protein Vpr arrests the cell cycle at G2 phase, which is important for efficient viral replication in dividing CD4+ T cells, because the transcriptional activity of the HIV-1 long terminal repeat is most active in G2 phase. Additionally, Vpr-mediated G2 arrest likely correlates with enhanced HIV-1 infection in monocyte-derived macrophages.
Results: Here, we screened small-interfering RNA to reveal candidates that suppress Vpr-induced G2 arrest and identified Huntingtin-interacting protein 1 (HIP1) as both directly interacting with Vpr and required for efficient G2 arrest. Interestingly, HIP1 was not essential for Vpr-induced DNA double-strand breaks, which are required for activation of the DNA-damage checkpoint and G2 arrest. Furthermore, HIP1 knockdown suppressed HIV-1 infection in monocyte-derived macrophages.
Conclusions: These results suggest that HIP1 operates in the downstream step(s) of DNA-damage induction to promote Vpr-induced G2 arrest and enhances HIV-1 infection in macrophages.
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Posted 17 Sep, 2020
On 04 Oct, 2020
Received 03 Oct, 2020
Received 30 Sep, 2020
Received 29 Sep, 2020
On 16 Sep, 2020
Invitations sent on 15 Sep, 2020
On 15 Sep, 2020
On 15 Sep, 2020
On 13 Sep, 2020
On 12 Sep, 2020
On 12 Sep, 2020
On 11 Sep, 2020
Huntingtin-interacting Protein 1 Promotes Vpr-induced G2 Arrest and HIV-1 Infection in Macrophages
Posted 17 Sep, 2020
On 04 Oct, 2020
Received 03 Oct, 2020
Received 30 Sep, 2020
Received 29 Sep, 2020
On 16 Sep, 2020
Invitations sent on 15 Sep, 2020
On 15 Sep, 2020
On 15 Sep, 2020
On 13 Sep, 2020
On 12 Sep, 2020
On 12 Sep, 2020
On 11 Sep, 2020
Background: Human immunodeficiency virus type 1 (HIV-1) modulates the host cell cycle. The HIV-1 accessory protein Vpr arrests the cell cycle at G2 phase, which is important for efficient viral replication in dividing CD4+ T cells, because the transcriptional activity of the HIV-1 long terminal repeat is most active in G2 phase. Additionally, Vpr-mediated G2 arrest likely correlates with enhanced HIV-1 infection in monocyte-derived macrophages.
Results: Here, we screened small-interfering RNA to reveal candidates that suppress Vpr-induced G2 arrest and identified Huntingtin-interacting protein 1 (HIP1) as both directly interacting with Vpr and required for efficient G2 arrest. Interestingly, HIP1 was not essential for Vpr-induced DNA double-strand breaks, which are required for activation of the DNA-damage checkpoint and G2 arrest. Furthermore, HIP1 knockdown suppressed HIV-1 infection in monocyte-derived macrophages.
Conclusions: These results suggest that HIP1 operates in the downstream step(s) of DNA-damage induction to promote Vpr-induced G2 arrest and enhances HIV-1 infection in macrophages.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5