Role of Innate Genes in HIV Replication

Abstract

Cells use an elaborate innate immune surveillance and defense system against virus infections. Here, we discuss recent studies that reveal how HIV-1 is sensed by the innate immune system. Furthermore, we present mechanisms on the counteraction of HIV-1. We will provide an overview how HIV-1 actively utilizes host cellular factors to avoid sensing. Additionally, we will summarize effectors of the innate response that provide an antiviral cellular state. HIV-1 has evolved passive mechanism to avoid restriction and to regulate the innate response. We review in detail two prominent examples of these cellular factors: (i) NLRX1, a negative regulator of the innate response that HIV-1 actively usurps to block cytosolic innate sensing; (ii) SAMHD1, a restriction factor blocking the virus at the reverse transcription step that HIV-1 passively avoids to escape sensing.

Hepatitis B Virus DNA is a Substrate for the cGAS/STING Pathway but is not Sensed in Infected Hepatocytes

“…In hepatic cells, STING expression is generally lower than in MDDCs, although it is always above the detection limit. Gamma-interferon-inducible protein 16 (IFI16), proposed as an immune sensor of retroviral DNA intermediates and a cGAS cooperative factor for activating STING [52], is expressed in PHH and HepaRG-hNTCP, although it is slightly reduced compared to immune cells, but is undetectable in the HepG2-derived cell lines. PQBP1, a cofactor of the cGAS/STING pathway involved in sensing HIV-1 reverse-transcribed DNA [53], is expressed to similar levels in all tested cell types.…”

The Dynamic Interplay between HIV-1, SAMHD1, and the Innate Antiviral Response

“…Expression of SAMHD1 can increase the susceptibility of HIV-1 to nucleoside reverse transcriptase inhibitors by reducing the levels of competitive dNTPs ( 106 – 109 ), suggesting modulation of SAMHD1 function may be a means to enhance drug effectiveness. Conversely, as SAMHD1 expression enables immune evasion by HIV-1 ( 13 ), it is tempting to hypothesize that SAMHD1 could be used as a drug target to enhance the innate immune response to viral infection. However, research is just beginning to uncover mechanisms to modify the dNTPase activity of SAMHD1 ( 110 , 111 ).…”

“…However, these cells are less permissive to HIV-1 infection compared to activated CD4 + T-cells, mainly due to host restriction factors that control the establishment or spread of viral infection. Several host proteins can restrict HIV-1 at various points in the viral lifecycle, including APOBEC proteins, TRIM5α, and tetherin ( 11 – 13 ). However, HIV-1 can exploit innate immune cells and their cellular factors to avoid detection and clearance by the host immune system ( 13 ).…”