Recent 5-year Findings and Technological Advances in the Proteomic Study of HIV-associated Disorders

Abstract

Human immunodeficiency virus-1 (HIV-1) mainly relies on host factors to complete its life cycle. Hence, it is very important to identify HIV-regulated host proteins. Proteomics is an excellent technique for this purpose because of its high throughput and sensitivity. In this review, we summarized current technological advances in proteomics, including general isobaric tags for relative and absolute quantitation (iTRAQ) and stable isotope labeling by amino acids in cell culture (SILAC), as well as subcellular proteomics and investigation of posttranslational modifications. Furthermore, we reviewed the applications of proteomics in the discovery of HIV-related diseases and HIV infection mechanisms. Proteins identified by proteomic studies might offer new avenues for the diagnosis and treatment of HIV infection and the related diseases.

Keywords: HIV-1; Interaction; Proteomics; SILAC; iTRAQ.

Figure 1

Summary of current proteomic technologies and their applications in the study of HIV infection A lot of proteomic technologies including gel-based, label or label-free proteomics are available for discovering diagnosis biomarkers and analyzing molecular mechanisms underlying HIV infection using samples such as body fluid, cells, and tissues. BALF, bronchoalveolar lavage fluid; CVL, cervicovaginal lavage; CER, Weck-Cel cervical sponge; PBMC, peripheral blood mononuclear cells; MDM, monocyte-derived macrophages; PM, plasma membrane; 2DE-MS, 2-dimensional electrophoresis mass spectrometry; SDS-PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis; iTRAQ, isobaric tags for relative and absolute quantitation; TMT, isobaric mass tagging; SILAC, stable isotope labeling by amino acids in cell culture; PTM, posttranslational modification; AP-MS, affinity purification-mass spectrometry; HIV, human immunodeficiency virus.

Figure 2

Summary of the identified proteins involved in HIV life cycle and subcellular localizations up- and down-regulations reviewed in this work Many host proteins get involved during HIV life cycle. Host proteins showing upregulated expression and downregulated expression upon HIV infection are indicated with ↑ and ↓, respectively. The image was modified from . Vpu, viral protein U; SNAT1, sodium coupled neutral amino acid transporter 1; CD, cluster of differentiation; PIC, pre-integration complex; TSG101, tumor susceptibility gene 101 protein; HIV, human immunodeficiency virus; Gag, group-specific antigen; STAT3, signal transducer and activator of transcription 3; ZAP70, zeta-chain-associated protein kinase 70; CK2α, casein kinase 2α; RT, reverse-transcription.

Figure 3

The body map showing different HIV-associated disorders and the reported proteins HRF, HIV-related fatigue; HL, Hodgkin’s lymphoma; HRLD, HIV-related lung disorder; HAND, HIV-associated neurocognitive disorder; HRCD, HIV-related cardiovascular disorder; HRRD, HIV-related renal disease; ApoA1, apolipoprotein A-1; AHSG, alpha-2-HS-glycoprotein; AMPB, aminopeptidase B; APOC1, apolipoprotein C-1; CCL2, C–C motif chemokine 2; CXCL10, C-X-C motif chemokine 10; S100-A9, S100 calcium binding protein A9; MHC, myosin heavy-chain; RyR1, ryanodine receptor 1.

Figure 4

Virus-host interactions summarized in this work The red, green and blue squares indicate the up-regulated, down-regulated, and interactive proteins of host, respectively. MAP4, microtubule-associated protein 4; KARS, lysyl-tRNA synthetase; DDX17, DEAD-box helicase 17; RPS6, ribosomal protein S6; PSGL, P-selectin glycoprotein ligand 1; Gag, group-specific antigen; Pol, DNA polymerase; Vif, virion infectivity factor; Vpr, viral protein regulatory; Vpu, virus protein U; Rev, regulator of expression of virion proteins; Env, envelope glycoprotein gp160; Tat, tyrosine aminotransferase; Nef, neferine; HSP90b, heat shock protein 90-beta; STAT3, signal transducer and activator of transcription 3; pRb, retinoblastoma-associated protein; CK2α, casein kinase II subunit alpha; ALG-2, apoptosis-linked gene-2; EHD4, EH domain-containing protein 4;; EIF5A-1, eukaryotic translation initiation factor 5A-1; GLUD2, glutamate dehydrogenase 2; AK2, adenylate kinase 2; HK, hexokinase; G6PD, glucose-6-phosphate dehydrogenase; PKM2, pyruvate kinase M2; FH, fumarate hydratase; TKT, transketolase.