Table 1.

Interactions among proteins of HIV and HCV (relevance for HCV/HIV coinfection models).

HCV proteins	Effect on HIV replication
NS3/NS4A	It interacts with HIV-1 Vpu promoting HIV transcription. Vpu facilitates degradation of NS3/4A and nuclear transfer of NS3 which can activate HIV-1 transcription [36].
Core	It restricts HIV-1 transcription and modulates viral replication in a hepatoma cell line through a repression before accumulation of threshold levels of Tat protein [63].
	It downregulates HIV LTR activity, in presence of high TNF-α level [3].
	It activates the TRAF pathway interacting with HIV-1 Nef, activating the NF-κB pathway via TRAF2, TRAF5, and TRAF6 pathways, and enhancing HIV-1 replication in macrophages [64].
	It induces HIV-1 reactivation in U1 cells through TNF-α and IL-6 [12].
HIV proteins	Effect on HCV replication
gp120	It enhances HCV replication in a CXCR4 or CCR5 engagement-dependent manner [9–11, 31, 34–36, 38–40, 65].
Rev	It increases gene expression of HCV by binding to the first internal loop (IIIb) of 5′-Untranslated Region and sites IRES of HCV RNA [42].
Tat	It activates HCV replication by upregulating IP-10 [47].
Nef	It exerts stimulatory effects on HCV replication, modifying the size and numbers of lipid droplets, increasing ROS, and, possibly, accelerating progression of liver disease [51–53].
Vpr	It enhances activity of 5′-Untranslated Region of HCV through stimulation of TATA box in the miR-122 promoter, upregulating miR-122 expression [55, 59, 60].

HCV: Hepatitis C Virus; HIV-1: Human Immunodeficiency Virus 1; NS: Nonstructural protein; CXCR4: C-X-C chemokine receptor type 4; CCR5: C-C chemokine receptor type 5; IRES: Internal Ribosome Entry Site; LTR: Long Terminal Repeat; TNF-α: Tumor Necrosis Factor alfa; IP-10: interferon gamma-induced protein 10; TRAF: TNF Receptor Associated Factor; NF-κB: Nuclear Factor κB; ROS: Reactive Oxygen Species; U1: HIV-1 latently infected U1 monocytic cell line; IL: Interleukin; miR: microRNA.