Phages and HIV-1: From Display to Interplay
Abstract
:1. Introduction
- Epitope mapping, which relies on the screening of random peptide libraries on immobilized monoclonal or polyclonal antibodies to determine the linear and/or conformational epitopes recognized by these antibodies (linear epitope: sequence of continuous amino acids recognized by the paratope of a given antibody; conformational/discontinuous epitope: group of amino acids scattered along a protein sequence which come together in the folded protein and are recognized by the paratope of a given antibody). Such screening usually results in the identification of sequences mimicking the natural epitope (mimotopes) and provides precise information about the location of residues forming the natural epitope. These mimotopes may in turn be used as valuable immunogens to elicit antibodies targeting the original epitope, an approach referred to as “reverse vaccinology”.
- Inhibitor discovery, based on screening of phage libraries displaying random peptides or antibody fragments against viral or host proteins critical for viral replication.
- “Phage Substrate” approach in which potential substrate sequences are displayed at the phage surface to enzymes such as proteases. This approach not only allows for proteolysis specificity profiling, but provides information and data to develop specific inhibitors.
- Carrier phage, in which the phage functions as a “carrier”, “vehicle” or “virus-like particle” to display exogenous peptides such as mimotopes or even full size antigens to the immune system, to elicit specific humoral and/or cytotoxic T-cells responses.
2. Exploration of HIV-1 Epitope Landscape
2.1. Antibodies Directed against Viral Proteins
2.1.1. Monoclonal Antibodies Directed against Viral Epitopes
2.1.1.1. Gp120 V3 Loop
2.1.1.2. Gp41 Membrane Proximal External Region (MPER)
2.1.1.3. Gp120 C1 Domain
2.1.1.4. Gp120 CD4-Binding Site
2.1.1.5. Other Domains
2.1.2. Polyclonal Antibodies Directed Against Viral Epitopes
2.2. Antibodies Directed against Host Proteins
3. Identification of HIV-1 Inhibitors by Phage Display
3.1. Inhibitors of HIV-1 Proteins
3.1.1. Env Inhibitors
3.1.1.1. Gp120 CD4 Binding Site
3.1.1.1.1. Fab Libraries
3.1.1.1.2. ScFvs Hydrolyzing gp120
3.1.1.1.3. Nanobodies
3.1.1.1.4. CD4 Mimics
3.1.1.2. Gp120 V3 Loop
3.1.1.3. Gp120 CD4-Induced Epitope
3.1.1.4. Gp120 C1 Domain
3.1.1.5. Phage Display as a Tool to Unravel the HIV-1-Specific Humoral Response
3.1.1.6. Gp41 MPER Inhibitors
3.1.1.7. Gp41 Heptad Repeat Inhibitors
3.1.2. Other HIV-1 Proteins
3.1.2.1. Viral Protein of Regulation (Vpr)
3.1.2.2. Integrase (IN)
3.1.2.3. Transactivator of Transcription (Tat)/Transactivation Response element (TAR)
3.1.2.4. Nucleocapsid (NC)/Packaging Signal (psi) Sequence
3.1.2.5. Negative Factor (Nef)/Virion Infectivity Factor (Vif)
3.1.2.6. Reverse Transcriptase (RT)
3.1.2.7. Regulator of Virion Expression (Rev)
3.1.2.8. Group-Specific Antigen (Gag)
3.1.3. Diagnostic Applications
3.2. Inhibitors of Host Proteins
3.2.1. Host receptors inhibitors
3.2.1.1. CCR5 Coreceptor
3.2.1.2. CXCR4 Coreceptor
3.2.2. Other Host Protein Inhibitors
4. Phage Substrate
5. Phage particles as HIV-1 Antigen Carriers
6. Conclusions and Future Challenges
Acknowledgements
Abbreviations
AA | amino acids |
Ab | Antibody |
ADCC | Antibody-Dependent Cellular Cytotoxicity |
AIDS | Acquired ImmunoDeficiency Syndrome |
ARM | Arginine Rich Motif |
BNtAb | Broadly Neutralizing Antibody |
BS | Binding Site |
BSA | Bovine Serum Albumin |
CCR5 | CC chemokine Receptor 5 |
CD | Cluster of Differentiation |
CDR | Complementarity Determining Region |
CH | Constant Heavy chain domain |
CHR | C-terminal Heptad Repeats |
CTL | Cytotoxic T-Lymphocytes |
CXCR4 | CXC chemokine Receptor 4 |
DDDP | DNA-Dependent DNA Polymerase |
ECL | ExtraCellular Loop |
Fab | Fragment antigen-binding |
FIV | Feline ImmunoDeficiency Virus |
FR | Frameworks |
Gag | group-specific antigen |
gp | glycoprotein |
HAART | Highly Active Anti-Retroviral Therapy |
HB | Helix Bundle |
HcAb | Heavy-chain only Antibody |
HCDR | Heavy-chain Complementarity Determining Region |
HIV-1 | Human ImmunoDeficiency Virus |
HLA | Human Leukocyte Antigen |
HOC | Highly antigenic Outer Capsid protein |
IC50 | Inhibitory Concentration 50 |
ID | Immuno Dominant |
ID50 | Inhibitory Dose 50 |
Ig | Immunoglobulin |
IN | Integrase |
KD | dissociation constant |
KLH | Keyhole Limpet Hemocyanin |
LTNP | Long-Term Non-Progressor |
MAb | Monoclonal Antibody |
MHC | Major Histocompatibility Complex |
MPER | Membrane Proximal External Region |
NC | NucleoCapsid |
NCp | Nucleocapsid protein |
Nef | Negative factor |
NHR | N-terminal Heptad Repeats; NLS, Nuclear Localization Signal |
NNY | n-nonanoyl |
NtAb | Neutralizing Antibody |
PAb | Polyclonal Antibody |
PBL | Peripheral Blood Lymphocytes |
PBMC | peripheral blood mononuclear cell |
PHI | PreHairpin Intermediate |
PIC | PreIntegration Complex |
PIE | Pocket-specific Inhibitor of Entry |
PR | Protease |
psi | packaging signal |
RDDP | RNA-Dependent DNA Polymerase |
Rev | Regulator of virion expression |
RPL | Randomized Peptide Library |
RT | Reverse Transcriptase |
ScFv | Single-chain variable fragment |
SOC | Small Outer Capsid protein |
SPR | Surface Plasmon Resonance |
TAR | Transactivation Response element |
TCR | T-Cells Receptor |
TRM | Tat/TAR Recognition Motif |
UDG | Uracyl DNA Glycosylase |
VH | Variable Heavy chain domain |
VHH | Variable Heavy-chain domains of Heavy-chain only Antibodies |
Vif | Virion infectivity Factor |
VL | Variable Light chain domain |
vpr | Viral Protein of Regulation |
VLP | Virus-Like Particle. |
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Target | Library | Target presentation | Mimotopes | Epitopes | Additional | Vaccination attempts | Results | Reference |
---|---|---|---|---|---|---|---|---|
MAb447-52D |
|
| GPxR | gp120 V3 loop | NA | Rabbit immunization with 1 peptide | NAbs induced | [17,18] |
MAb 58.2 | 20-mer RPL |
| (Y/L)(V/L/I)GPGRxF | gp120 V3 loop | Characterization of non-essential aminoacids in the epitope using a peptide array | NA | NA | [19] |
MAb 19B | 15-mer RPL | Ab captured on polystyrene beads | xIx4GxxFYxT | gp120 V3 loop | Type II β turn structure of the epitope | NA | NA | [18,20] |
MAb 1001 | 30-mer RPL | Ab coated onto microwells | (R/K/H)xGR | gp120 V3 loop | Peptides fused to E. coli AP. Affinities for the Ab determined by SPR | NA | NA | [21] |
| 6-mer RPL | NA |
| gp120 V3 loop | QR insertion characteristic of the LAI isolate | NA | NA | [22] |
MAb 268 | 6-mer RPL | Biotinylated Ab captured on streptavidin-coated beads | 268.1 (HLGPGR), 268.2 (KAIHRI) | gp120 V3 loop | NA | Rabbit immunization | gp120-specific Abs | [23] |
MAb 2F5 | 15mer | Ab captured on polystyrene beads | ELDKW, D(K/R)W | ELDKWA (gp41 MPER) | 2F5 affinity for gp41 and gp41 peptide determined by SPR | NA | NA | [24] |
MAb 2F5 | 17 constrained and linear RPL, x12-AADKW and AADKW-x12 sublibraries | Biotinylated Ab captured on streptavidin-coated beads | 3 peptides (AADKW-x12) | ELDKWA (gp41 MPER) | Ala substitutions and deletions studies | NA | NA | [25] |
MAb 2F5 | 12-mer and 7-mer-c RPL | Ab coated onto microwells | DKWA, LDKWA | ELDKWA (gp41 MPER) | Epitope specificity depends on the structural context of the library | Mice and rabbit immunization | Inhibition of cell fusion | [26] |
| 20-mer RPL | Rabbit anti-mouse IgG, Fc-specific Ab coated on Petri dishes |
| C1 domain of gp120 | Pepscan analysis, quantitative binding analysis | NA | NA | [27] |
MAb ID6 | 12-mer, 7-mer, 7-mer-c RPL | Mab captured on rat anti-mouse Ab coated microwells | TxxFxxWxxD, FxDWxF | C1 domain of gp120 | ADCC-inducing Ab | NA | NA | [28] |
MAb b12 |
| Biotinylated IgG1b12 captured on avidin-coated microwells |
| gp120 CD4 binding site | Competition with gp120 for the binding to IgG1b12, determination of the in-solution binding affinity. | (2) Phage B2.1 immunization of mice and rabbits | Anti-peptide Abs elicited | [29,30] |
MAb b12 | x10ALLRYx10, x3(M/V)WSDx3 and xLXVWxDExx RPL | Ab coated onto tubes | GLLVWSDEL | gp120 CD4 binding site | NA | Mice immunization | Env-specific Abs | [31] |
MAb b12 | 12-mer-c RPL | Ab captured on Protein G-coated Petri dishes | WSDL | gp120 CD4 binding site | Prediction of epitope clusters with Mapitope | NA | NA | [32] |
MAb 5145A | 9-mer and 10-mer-c RPL | Ab coated onto Petri dishes | AECGPAEPRGAWVC, AECGPYEPRGDWTCC | gp120 CD4 binding site | NA | Rabbit immunization with peptides-HSP fusion constructs | gp120-specific Abs elicited, recognizing a different epitope | [33] |
MAb 803-15.6 | 7-mer RPL |
| AxxKxRH | gp120 residues 502–508 | Quantitative binding analysis | NA | NA | [34] |
| 12-mer-c RPL | Ab captured on Protein G-coated Petri dishes | NA |
| Prediction of epitope clusters with Mapitope | NA | NA | [32] |
| 15-mer RPL | Ab captured on polystyrene beads |
|
| NA | NA | NA | [18] |
MAb 2G12 | Set of RPL | Ab captured on protein A-coated beads | 2G12.1 (ACPPSHVLDMRSGTCL) | Glycosylated gp120 | NA | Rabbit immunization | No HIV-specific Abs | [35] |
Library | Biopanning support | Samples | Target | Biopanning procedure | Mimotopes | Epitopes | Additional | Vaccination attempts | Results | Reference |
---|---|---|---|---|---|---|---|---|---|---|
9-mer, 9-merc RPLs | Tosylactivated beads coupled to Anti human IgG, Fc-specific Ab | LTNP (serum) | IgG | Panning on one LTNP, reactivities assessed on a second LTNP | 3 linear, 7 putative conformational | Linear: gp41 ID GKLIC region, gp120 V1 and C2 regions | Reactivities of positive clones assessed on 22 LTNP, 25 HIV, 50 HD. Affinity purification of Nabs with phages | Phage immunization of C57BL and BalB/c mice | NAbs induced | [50] |
12-mer-c RPL | Protein G coated on Petri dishes | HIV + (serum) | IgG | Panning on HIV+ serum IgG | 4 linear, 2 unassigned | Linear: gp41 ID GKLIC region | Reactivities of the clones assessed on the sera of 30 HIV+ | NA | NA | [52] |
12-mer, 7- mer, 7-mer-c RPLs | Microwells coated with purified IgG | HIV+ (HAART) | IgG | Panning on purified HIV+ IgG, before and after HAART | Linear, CxxKxxC | Linear: gp41 ID GKLIC region | Reactivities of 1 insert with IgG of 22 HIV+ | Phage immunization of C57BL/6J mice | Abs against epitope | [53] |
12-mer, 7- mer, 7-mer-c RPLs | Tosylactivated beads coupled to Anti human IgG, Fc-specific Ab | LTNP (plasma) | IgG | Panning on pool of 8 LTNP plasma, negative selection on HIV - plasma pool | 160 linear, 124 putative conformational, 160 unassigned | gp120 V3 loop, gp41 GKLIC, gp120 MPER | Reactivities with plasma of 7 HIV+ plasma | Phage immunization of mice | NAbs induced | [54] |
12-mer, 7- mer, 7-mer-c RPLs | Tosylactivated beads coupled to Anti monkey IgG Ab | Clade C SHIV-infected rhesus macaque | IgG | Panning on one SHIV + plasma, negative selection on SHIV - monkey plasma pool | 72 linear, 6 putative conformational | gp120 V2, V3, C-term, gp41 GKLIC, MPER | Reactivities of inserts tested as fusion proteins | DNA prime-phage boost of BALB/c mice | NAbs induced | [55] |
12-mer RPL | Tosylactivated beads coupled to Anti human IgG, Fc-specific Ab | HIV subtype CRF02AG-infected plasma with 4E10-like BNtAbs | IgG | Panning on pooled longitudinal samples of one HIV + plasma, negative selection on HIV - plasma pool | Linear (SLxxLRL, KxWWxA, Kx3IGPHxxY) | gp41 MPER and LLP2 regions; gp120 C1 and V3 regions | NA | NA | NA | [56] |
12-mer, 7- mer, 7-mer-c RPLs | Tosylactivated beads coupled to Anti human IgG, Fc-specific Ab | HIV subtype A-infected plasma with 4E10-like BNtAbs | IgG | Panning on pooled longitudinal samples of one HIV + plasma, negative selection on HIV - plasma pool | 38 linear, 22 putative conformational (Kx3Hx3Y, KxxHxGPx3F, CxGxLxCTxNxP) | gp41 ID epitope; gp120 V2 and V3 regions | Competition with rgp120/gp140 for antibodies binding; peptide neutralization inhibition assays | NA | NA | [57] |
DNAse-fragmented Gag DNA | Purified IgG captured on microwells | Serum of rabbits immunized with p24 | IgG | Panning on rabbit anti p24 IgG | p24 fragments | N- and C-terminus of p24 | Reactivities of inserts tested as proteins in fusion with GST | NA | NA | [58] |
Target | Library | Target presentation | Mimotopes | Epitopes | Additional | Vaccination attempts | Results | Reference |
---|---|---|---|---|---|---|---|---|
MAbs 3A9, 5C7 | 7-mer, 7-mer-c, 9-mer-c, 12-mer RPL | Phage-antibody complexes captured on beads coated with anti-mouse IgG Ab | CHASIYDFGSC, CPHWLRDLRVC | CCR5 N-terminus (SIYD) and ECL1 (FG) CCR5 N-terminus (P), ECL1 (HW) and ECL3 (DLR) | Reactivities assessed against inserts synthesized as peptides, binding and competition assays with peptides. Entry inhibitor | NA | NA | [62,63] |
MAb 2D7 | 15-mer RPL | Ab coated onto Petri dishes | M23 (FCALDGDFGWLAPAC) | CCR5 ECL2 | Neutralization of HIV-1 infection | NA | NA | [64] |
MAb 2D7 | 12-mer RPL | Ab coated onto microwells | EWQKEGLVTLWL | CCR5 ECL2 | NA | Rabbit immunization | NAbs with 2D7-like functions | [65] |
MAb MHM23 | 9-mer, 9-mer-c RPL | Phages-Ab complexes captured on streptavidin-coated dishes | PPFxYRK | CD18 (AA 200–206) | Inhibition of HIV-1-induced syncytium formation | NA | NA | [66] |
Target | Library | Target presentation | Phagotopes | Affinity (KD) | Inhibition (IC50) | Virus isolates/clades | Additional | Reference |
---|---|---|---|---|---|---|---|---|
gp120 (CD4 BS) | LTNP Fab | Recombinant gp120 | b12 | <10 nM | ~20 nM | MN, IIIb | NA | [41,42,70] |
gp120 (CD4 BS) | Fab (CDR walking of b12 Fab) | Recombinant gp120 | 3D3 | 15 pM | ~0.1–0.9 nM | MN, IIIb | 3B3 ScFv engineered as fusion immunotoxin | [71–73] |
gp120 (CD4 BS) | LTNP Fab | Recombinant gp120 | L78 | 4–300 nM | ~2 ug/mL | MN, IIIb | epitope-masking strategy | [74] |
gp120 (CD4 BS) |
| Recombinant gp120 | JL413 SKL6 | NA |
|
| gp120-hydrolyzing Abs | [75,76] |
gp120 (CD4 BS) | VHH (immunized llamas) | Recombinant gp120 | A12 D7 C8 | 0.1–1 nM | 0.003–38 μg/mL | A, B, C, D, CFR02_AG and CRF07_BC | sublibrary engineered to increase potency | [77,78] |
gp120 (CD4 BS) | CD4 V1 and V1-V2 variants | Recombinant gp120 | E6, B6, 22, F8, D11 | NA | 0.2–1 μg/mL | BH10 | NA | [79] |
gp120 (V3 loop) | MAb 447-52D-derived ScFv | V3 loop peptide | 402P5H7 | 0.28–3.1 nM | NA | MN | VL shuffling and HCDR3 “spiking” of MAb 447-52D | [80] |
gp120 (V3 loop) | LTNP Fab | Recombinant gp120 | DO142-10 Fab loop 2 | 11 nM 1.9 nM | 0.2–8 μg/mL 1–5 μg/mL | MN, IIIb | epitope-masking strategy | [70,81] |
gp120 (CD4-i epitope) | 7-mer, 9-mer-c and 12-mer RPL | Recombinant gp120 | 12p1 | NA | 1.1–1.6 μM | YU2 | NA | [82] |
gp120 (CD4-i epitope) | HIV-1 infected FDA-2 patient FAb | gp120-CD4-CCR5 complexes | X5 | nanomolar | 0.29–125 μg/mL | A, B, C, D, F and G | NA | [83] |
gp120 (CD4-i epitope) | 7-mer, 7-mer-c and 12-mer RPL | sCD4-89.6 Env on retroviral particles | XD3 | NA | 50 μM | NL4-3, D117III | NA | [84] |
gp41 MPER |
| MPER peptide |
| NA |
| B, C and E | NA | [85] [86] |
gp41 Heptad Repeats |
|
|
| NA |
|
| (1) D-peptide | [87–89] [90,91] [92] [93,94] |
gp41 Heptad Repeats | (1), (2) Naïve human Fabs (3) Fab 3674-derived Fabs |
|
|
|
|
| NA | [95] [96–98] |
gp41 Heptad Repeats |
|
|
| NA |
|
| (2) competitive antigen panning | [99] [100–102] |
Vpr |
|
|
| NA | NA | NA |
| [103] [104] |
Int | 7-mer RPL | Recombinant Int | FHNHGKQ | NA | NA | NA | Inhibition of strand transfer activity | [105] |
|
|
|
|
| NA | NA | (2) inhibition of Tat-mediated transactivation and HIV-1 replication when transfected | [106] [107] [108] |
|
|
|
| NA | NA | NA | (2) reduction of virus release by infected cells | [109] [110–112] |
|
|
|
| (1) 2nM | NA | NA | (2) inhibition of HIV- 1 replication | [113–115] [116,117] |
RT |
| Recombinant RT |
| NA | NA | NA | Inhibition of RDDP and/or DDDP activity | [118,119] [120] |
Rev |
| Rev |
| NA | NA | NA | NA | [106,121–124] |
Gag | 12-mer RPL | CA protein (AA 162–190) | CAI | NA | NA | NA | In vitro inhibition of capsid assembly | [125] |
Target | Library | Target presentation | Biopanning procedure | Phagotope | Affinity | Inhibition | Virus isolates/clades | Additional | Reference |
---|---|---|---|---|---|---|---|---|---|
CCR5 | Human ScFv | Liposome | Five rounds | NA | NA | NA | NA | NA | [180] |
CCR5 | Human VH-Rabbit ST6 HCDRs | CCR5 Nterm-GST fusion | Four rounds, acidic elution | Rabbit ST6 Human ST6/34 | 2.7 nM 8.5 nM | NA | NA | Inhibit CCR5 export when expressed as intrabodies | [184] |
CCR5 | Randomized and extended CCL5 chemokine | HEK-CCR5, CHO-CCR5 | Recovery of internalized phages, acidic elution | CCL5 P1-CCL5 P2-CCL5 | IC50 = 4.1 nM IC50 = 2 nM IC50 = 0.2 nM | NA IC50 = 7.0 nM IC50 = 0.6 nM | BaL | P1: triggers reduced signaling P2: superagonist inducing CCR5 sequestration | [185] |
CCR5 | Randomized and extended CCL5 chemokine | HEK-CCR5, CHO-CCR5 cells | Recovery of internalized phages, acidic elution | 6P4-CCL5 5P12-CCL5 5P14-CCL5 | NA NA NA | IC50 = 21 pM IC50 = 28 pM IC50 = 26 pM | BaL | Superagonist + sequestration No signaling + no sequestration Internalization + no signaling | [186] |
CCR5 | Mice and rats ScFV | ECL1, ECL2, ECL3 biotinylated peptides | Alkaline elution | A1 (ECL1) B7 (ECL2) L9 (ECL2) | NA NA NA | 25% a 35% a 25% a | BaL | All active ScFv were selected on cyclic peptides | [181] |
CCR5 | 12-mer RPL | CHO-CCR5 cells | Four rounds, acidic elution | AFDWTFVPSLIL | IC50 = 2.5 μM | NA | NA | Antagonist of CCR5 | [179] |
CCR5 | Partially randomized
| CHO-CCR5 cells |
|
| NA | No inh IC50 = 2.5 μM | ADA | Does not act as CCR5 agonist or antagonist | [178] |
CXCR4 | Llamas immunized VHH | HEK-CXCR4 cells | Two rounds and counterselection | 238D2 238D4 238D2-15GS-238D4 | KI = 10 nM KI = 6 nM KI = 0.3 nM | IC50 = 30 nM IC50 = 40 nM IC50 = 0.2 nM | NL4.3 | Inhibit chemotaxis and mobilize stem cells | [187] |
CXCR4 | Non immunized HCDR3 | Linear ECL2 peptide | Four rounds, acidic elution | YYCARDRGGTYPGR YWCQG | KD = 5 μM | NA | NA | Antagonist of CXCR4 | [182] |
CD40 | Human ScFv | Biotinylated CD40-Fc fusion protein | Four rounds, trypsin elution | B44 | KD = 60 nM | 3–4 fold reduction of infection | R5- tropic | Activates normal B cells, Does not block CD40- CD40L binding | [188,189] |
DDX3 | Mix of 12-mer and 7- mer RPL | His tagged ALRAMKENGR peptide | Acidic elution | INS1: SDVPTQVGGRRRRRRRRR | NA | IC50 = 20 μM | LAI | Homologies to XPO1/CRM1 | [190] |
Target | Library | Biopanning | Natural substrates P4-P3-P2-P1--P1′-P2′-P3′-P4′ | Selected substrates | Kcat/Km (μM−1s−1) | Derived Inhibitors | KI (nM) | Reference |
---|---|---|---|---|---|---|---|---|
HIV-1 protease Q7K | Random hexapeptides fused to the MAb 3-E7 epitope and displayed on Fd phage | 5 rounds with progressive decrease of the protease concentration and contact time | (RT/IN) RKIL↓FLDG (MA/CA) SQNY↓PIVQN (CA/P2) ARVL↓AEAM (P2/NC) ATIM↓MQRG (P1/P6) PQNF↓LQSR (in P6) KELY↓PLTS (TF/PR) SFNF↓PQIT (PR/RT) TLNF↓YVDG (in RT) AETF↓YVDG | GSGIF↓LETSL | 1.3 | [199] | ||
GSGVF↓VEMPL | 3.9 | GSGIFΨ (CH2NH)LETSL | 5 | |||||
GSGVF↓VVNGL | 18 | GSGVFΨ (CH2NH)VEMPL | 18 | |||||
GSGLF↓TEYGL | 0.002 | GSGVFΨ (CH2NH)VVNGL | 100 | |||||
IRKIL↓FLDG | 0.002 | GSGLFΨ (CH2NH)TEYGL | 200 | |||||
HIV-1/FIV proteases | 4 rounds with progressive decrease of the protease concentration | Protease | IC50 (nM) | [198] | ||||
SGNF↓VVNGLVK | HIV-1 only | |||||||
KSGVF↓VENGLVK | HIV-1 only | |||||||
KSGVF↓VQNGLVK | HIV-1 only | |||||||
KSGNFVVN↓GLVK | FIV only | |||||||
KSGV↓SVNGK | FIV only | |||||||
KSGVFHVN↓GLVK | FIV only | GSGVF Ψ (CH2OH)VVNGL | HIV/FIV | |||||
KSGVFQVN↓GLVK | FIV only | GSGVF Ψ (CH2NH)VVNGL | 160/5000 | |||||
KSGVF↓VVNGLVK | HIV-1/FIV | 700/400 | ||||||
KSFVF↓VVNGLVK | HIV-1/FIV | |||||||
KSGIF↓VVNGLVK | HIV-1/FIV | |||||||
KSGVF↓HVNGK | HIV-1/FIV | |||||||
KSGVF↓QVNGLVK | HIV-1/FIV | |||||||
KSGVF↓VVQGLVK | HIV-1/FIV | |||||||
KSGVF↓VVTGLVK | HIV-1/FIV |
P4 | P3 | P2 | P1 | P1′ | P2′ | P3′ | P4′ |
---|---|---|---|---|---|---|---|
S11 | G11 | V5 | Y5 | F4 | V5 | T4 | S3 |
I3 | F4 | V3 | E4 | S3 | T2 | ||
N3 | M2 | L3 | A1 | M1 | G2 | ||
H1 | Q1 | E1 | P1 | ||||
N1 | N1 | ||||||
Q1 | D1 | ||||||
A1 |
Phage | Type | Carrier protein | HIV-1 antigen | Display level | Animal Model | Reference |
---|---|---|---|---|---|---|
M13 | Filamentous | pIII | p17 (GEDRW) | 3 to 5 copies/phage | Rabbit | [205] |
fd | Filamentous | pIII | V3 loop of gp120 | 3 to 5 copies/phage | Mice | [207] |
fd | Filamentous | pIII | V3 loop of gp120 | 3 to 5 copies/phage | Mice | [210] |
fd | Filamentous | pVIII | RT (ILKEPVHGV) | 2700 copies/phage | Human cells | [206,214] |
M13 | Filamentous | pVIII | V3 loop variants | 2700 copies/phage | Mice | [215] |
T4 | Lytic/Icosahedral | SOC | V3 loop of gp120 | 960 copies/phage | Mice | [214] |
T4 | Lytic/Icosahedral | HOC | p24 | 150 copies/phage | Mice | [216] |
MS2 | VLP/Icosahedral | A-B loop | V3 loop of gp120 | 90 copies/VLP | Mice | [212] |
PP7 | VLP/Icosahedral | A-B loop | V3 loop of gp120 | - | Mice | [217] |
Lambda | Lytic/Icosahedral | gpD | gp140 trimer | 30 copies/phage | Rabbit | [213] |
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Delhalle, S.; Schmit, J.-C.; Chevigné, A. Phages and HIV-1: From Display to Interplay. Int. J. Mol. Sci. 2012, 13, 4727-4794. https://doi.org/10.3390/ijms13044727
Delhalle S, Schmit J-C, Chevigné A. Phages and HIV-1: From Display to Interplay. International Journal of Molecular Sciences. 2012; 13(4):4727-4794. https://doi.org/10.3390/ijms13044727
Chicago/Turabian StyleDelhalle, Sylvie, Jean-Claude Schmit, and Andy Chevigné. 2012. "Phages and HIV-1: From Display to Interplay" International Journal of Molecular Sciences 13, no. 4: 4727-4794. https://doi.org/10.3390/ijms13044727