SIV/SHIV-Zika co-infection does not alter disease pathogenesis in adult non-pregnant rhesus macaque model

Abstract

Due to the large geographical overlap of populations exposed to Zika virus (ZIKV) and human immunodeficiency virus (HIV), understanding the disease pathogenesis of co-infection is urgently needed. This warrants the development of an animal model for HIV-ZIKV co-infection. In this study, we used adult non-pregnant macaques that were chronically infected with simian immunodeficiency virus/chimeric simian human immunodeficiency virus (SIV/SHIV) and then inoculated with ZIKV. Plasma viral loads of both SIV/SHIV and ZIKV co-infected animals revealed no significant changes as compared to animals that were infected with ZIKV alone or as compared to SIV/SHIV infected animals prior to ZIKV inoculation. ZIKV tissue clearance of co-infected animals was similar to animals that were infected with ZIKV alone. Furthermore, in co-infected macaques, there was no statistically significant difference in plasma cytokines/chemokines levels as compared to prior to ZIKV inoculation. Collectively, these findings suggest that co-infection may not alter disease pathogenesis, thus warranting larger HIV-ZIKV epidemiological studies in order to validate these findings.

Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

“…We find that the type I IFN responses elicited in SIV-infected RMs correlates with reduced ZIKV replication, that these coinfected animals mount inferior humoral responses to ZIKV, and that these animals have delayed ZIKV clearance. A recent study, using a small cohort of simian-human immunodeficiency virus (SHIV)-and SIV-infected RMs also found that ZIKV viremia was uncharacteristically low during coinfection; however, the authors concluded that SHIV/SIV infections did not dramatically influence the course of ZIKV infection (64). This small study of only 4 Asian macaques used historical controls and did not study immune responses to ZIKV; thus, the study is somewhat difficult to interpret.…”

De Novo Isolation & Affinity Maturation of yeast-displayed Virion-binding human fibronectin domains by flow cytometric screening against Virions

“…Immediately following concentration of cell culture supernatants UC purification of Zika virions [33] was carried out using allopolymer tubes (Denville Scientific) and OptiPrep density Gradient Media (Sigma). 15 mL of 12% OptiPrep in PBS (vol/vol) was overlaid on 10 mL of 35% OptiPrep (vol/vol) in 38.5 mL allopolymer tubes and 1.5 mL of concentrated viral supernatant was overlaid onto the 12% OptiPrep layer.…”

Urinary cytokine measurements do not reflect surgery‐induced inflammation in rhesus macaques

“…A total of 33 different cytokines were measured in urine using the Luminex system (Table 1). All tested biomarkers have been successfully measured from plasma in prior studies of macaques (Bidokhti et al, 2018;Höglind et al, 2017;Joas et al, 2020;Olwenyi et al, 2022;Pantoja et al, 2017;Pérez-Guzmán et al, 2019;Singh et al, 2021;Woollard et al, 2018). The assay included evaluation of processed as described in Giavedoni (2005).…”

“…A total of 33 different cytokines were measured in urine using the Luminex system (Table 1). All tested biomarkers have been successfully measured from plasma in prior studies of macaques (Bidokhti et al, 2018; Höglind et al, 2017; Joas et al, 2020; Olwenyi et al, 2022; Pantoja et al, 2017; Pérez‐Guzmán et al, 2019; Singh et al, 2021; Woollard et al, 2018). The assay included evaluation of the following analytes: B‐cell activating factor (BAFF); B lymphocyte chemoattractant (BLC, CXCL13); C‐reactive protein (CRP); eotaxin‐1 (CCL11); granulocyte colony‐stimulating factor (G‐CSF); growth‐related oncogene‐a (GRO‐a, CXCL1); indoleamine‐pyrrole 2,3‐dioxygenase (IDO); interferon‐α (IFN‐α); IFN‐γ; interferon‐inducible T‐cell α chemoattractant (I‐TAC, CXCL11); interferon‐γ‐induced protein 10 kDa (IP‐10, CXCL10); interleukin‐1 beta (IL‐1β); IL‐1 receptor antagonist (IL‐1RA); IL‐4; IL‐8; IL‐10; IL‐12 p40 and p70; IL‐15; IL‐18; IL‐22; IL‐33 receptor (IL33R; ST2); lectin‐type oxidized low‐density lipoprotein receptor 1 (LOX‐1); macrophage migration inhibitory factor (MIF); monokine induced by γ interferon (MIG, CXCL9); macrophage inflammatory protein 1‐α (MIP‐1α, CCL3), MIP‐1β (CCL4); monocyte chemoattractant protein 1 (MCP‐1, CCL2); myeloperoxidase (MPO); perforin; regulated on activation, normal T cell expressed and secreted CCL5 (RANTES); tumor necrosis factor‐α (TNF‐α); soluble CD40 ligand (sCD40L); soluble intercellular adhesion molecule 1 (sICAM‐1); and vascular endothelial growth factor A (VEGF‐A).…”