Table 2.

Summary and key findings from studies investigating Vpr-induced neuroinflammation from astrocytes

Vpr status	Model	Markers Investigated	Assay	Key findings for marker levels	Other key findings	Ref
Viral protein R (Vpr)+	Human fetal astrocytes (HFAs)	Interleukin (IL)-6, IL-8, C–C motif chemokine ligand (CCL)-2 and migration inhibitor factor (MIF)	Cytokine Array	↑ IL-6, IL-8, C–CCL-2 and MIF	1. SK-N-SH neuroblastoma cells exposed to recombinant (r)Vpr or mutant rVpr (73R and 80 A) conditioned medium decreased synthesis of Glutathione and increased apoptosis	[26]
Vpr+	HFAs	CCL5	Polymerase chain reaction (PCR) and Immunocytochemistry	↑CCL5	1. Increased CCL5 induction mediated by transcription factors nuclear factor kappa B (NF-κB) and Activator protein (AP)-1 and involved the p38- Mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K)/Akt pathway.	[25]
Vpr+	HFAs	IL-6 and IL-8	Polymerase chain reaction (PCR)	↑IL-6 and IL-8	1. Increased levels of IL-6 and IL-8 were by the increased activation of transcription factors NF-κB, AP-1 and C/EBP-δ via upstream protein kinases PI3K/Akt, p38-MAPK and Jun N-terminal kinases (Jnk)-MAPK	[38]
Vpr+	Astrocytes	Toll-like receptor (TLR)4 and Tumour necrosis factor (TNF)-α,	Immunohistochemistry	↑ TLR4 and TNF-α	1. Vpr was colocalized with upregulated expression of TLR4, TNF-α, NF-κB, and sulfonylurea receptor 1 - Transient receptor potential (Trp) melastatin 4 (Sur1-Trpm4) in astrocytes of brain tissue from HIV-infected patients as well as in mice brain tissue. 2. Increased level of TLR4, TNF-α, NF-κB was by increased expression of Sur1-Trpm4 channel in astrocytes	[40]
Vpr+	Astrocytes	IL-6 and IL-1β	PCR	↓ IL-6 and IL-1β	1. Soluble Vpr was neurotoxic to primary human and rat fetal neurons in a concentration-dependent manner, as indicated by loss of β-tubulin expression 2. Findings for IL-1β levels from astrocytes were variable compared to monocytic cells 3. IL-6 were lower in both astrocytes and monocytic cells	[22]

The table is presented according to the findings presented in Sect. 3.3

Abbreviations: Activator protein (AP)-1, C–C motif chemokine ligand (CCL), Human fetal astrocytes (HFAs), Interleukin (IL), Migration inhibitor factor (MIF), Mitogen-activated protein kinase (MAPK), Nuclear factor kappa B (NF-κB), Phosphoinositide 3-kinase (PI3K), Polymerase chain reaction (PCR), Sulfonylurea receptor 1 -Transient receptor potential (Trp) melastatin 4 (SUR1-TRPM4), Toll-like receptor (TLR)4, Tumour necrosis factor (TNF)-α and Viral protein R (Vpr)+