Structure-function studies of the human immunodeficiency virus type 1 matrix protein, p17

Cannon, P M; Matthews, S; Clark, N; Byles, E D; Iourin, O; Hockley, D J; Kingsman, S M; Kingsman, A J

doi:10.1128/jvi.71.5.3474-3483.1997

Cited by 86HIV Research and TreatmentHIV/AIDS drug development and treatmentProtein Structure and Dynamics

Structure-function studies of the human immunodeficiency virus type 1 matrix protein, p17

Open access

Cannon, P M, Matthews, S, Clark, N, Byles, E D, Iourin, O, Hockley, D J, Kingsman, S M, Kingsman, A J·1997·Journal of Virology

DOI 10.1128/jvi.71.5.3474-3483.1997PMC PMC191494

Open this paper in CoChat — free account

Abstract

The human immunodeficiency virus type 1 (HIV-1) matrix protein, p17, plays important roles in both the early and late stages of the viral life cycle. Using our previously determined solution structure of p17, we have undertaken a rational mutagenesis program aimed at mapping structure-function relationships within the molecule. Amino acids hypothesized to be important for p17 function were mutated and examined for effect in an infectious proviral clone of HIV-1. In parallel, we analyzed by nuclear magnetic resonance spectroscopy the structure of recombinant p17 protein containing such substitutions. These analyses identified three classes of mutants that were defective in viral replication: (i) proteins containing substitutions at internal residues that grossly distorted the structure of recombinant p17 and prevented viral particle formation, (ii) mutations at putative p17 trimer interfaces that allowed correct folding of recombinant protein but produced virus that was defective in particle assembly, and (iii) substitution of basic residues in helix A that caused some relocation of virus assembly to intracellular locations and produced normally budded virions that were completely noninfectious.

Integrity signals

Registry

Crossref · 10.1128/jvi.71.5.3474-3483.1997

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Alterations in the MA domain of HIV-1 Gag, whether through amino acid substitutions or deletions, redirect virus assembly to the cytoplasm or intracellular membranes, such as the endoplasmic reticulum.
“alterations in the MA domain of HIV-1 Gag, whether through amino acid substitutions or deletions, have been shown to redirect virus assembly to the cytoplasm or intracellular membranes, such as the endoplasmic reticulum”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Cannon et al. 1997

Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1
Göttlinger, H. G., Sodroski, J. G., & Haseltine, W. A. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.15.5781 · Cited by 841 · see citing works
Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins
Gelderblom, H. R., Hausmann, E. H. S., Özel, M., Pauli, G., & Koch, M. A. (1987) · Virology · doi:10.1016/0042-6822(87)90449-1 · Cited by 521 · see citing works
Crystal structures of the trimeric human immunodeficiency virus type 1 matrix protein: implications for membrane association and assembly
Hill, C. P., Worthylake, D., Bancroft, D. P., Christensen, A. M., & Sundquist, W. I. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.7.3099 · Cited by 473 · see citing works
Role of the matrix protein in the virion association of the human immunodeficiency virus type 1 envelope glycoprotein
Dorfman, T., Mammano, F., Haseltine, W. A., & Göttlinger, H. G. (1994) · Journal of Virology · doi:10.1128/jvi.68.3.1689-1696.1994 · Cited by 288 · see citing works
Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein
Massiah, M. A., Starich, M. R., Paschall, C., Summers, M. F., Christensen, A. M., & Sundquist, W. I. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1719 · Cited by 271 · cited 4× · see citing works
“The core of p17 contains a hydrophobic pocket composed of residues V7, I34, A37, L41, L51, C57, I60, I82, and L85 (29, 30).”
BackgroundInfluential
A large deletion in the matrix domain of the human immunodeficiency virus gag gene redirects virus particle assembly from the plasma membrane to the endoplasmic reticulum
Fäcke, M., Janetzko, A., Shoeman, R. L., & Kräusslich, H. G. (1993) · Journal of Virology · doi:10.1128/jvi.67.8.4972-4980.1993 · Cited by 198 · see citing works
Crystal structure of SIV matrix antigen and implications for virus assembly
Rao, Z., Belyaev, A. S., Fry, E., Roy, P., Jones, I. M., & Stuart, D. I. (1995) · Nature · doi:10.1038/378743a0 · Cited by 183 · see citing works

Flagged first, then by citations

Sorted by citations

Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane
Ono, A., Ablan, S. D., Lockett, S. J., Nagashima, K., & Freed, E. O. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405596101 · Cited by 553 · see citing works
Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly
Saad, J. S., Miller, J., Tai, J., Kim, A., Ghanam, R. H., & Summers, M. F. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602818103 · Cited by 545 · see citing works
Endophilins interact with Moloney murine leukemia virus Gag and modulate virion production
Wang, M. Q., Kim, W., Gao, G., Torrey, T. A., Morse, H. C., Camilli, P. V. D., & Goff, S. P. (2003) · Journal of Biology · doi:10.1186/1475-4924-3-4 · Cited by 49 · see citing works
“Amino-acid substitutions or deletions in the matrix protein of type 1 human immunodeficieny virus (HIV-1) or Mo-MuLV were found to block membrane association [9-12] or to redirect virus assembly to cytoplasmic vacuoles (multivesicular bodies, MVBs).”
Background
Proteolytic refolding of the HIV‐1 capsid protein amino‐terminus facilitates viral core assembly
von Schwedler, U. K., Stemmler, T. L., Klishko, V. Y., Li, S., Albertine, K. H., Davis, D. R., & Sundquist, W. I. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1555 · Cited by 337 · see citing works
“…because even more severe viral assembly defects can be caused by mutations in other Gag domains, including MA (e.g. Kräusslich and Welker, 1996; Cannon et al., 1997), the carboxy-terminal domain of CA (e.g. Dorfman et al., 1994; Reicin et al., 1995, 1996) and NC (e.g. Jowett et al., 1992;…”
Background
Role of the Gag Matrix Domain in Targeting Human Immunodeficiency Virus Type 1 Assembly
Ono, A., Orenstein, J. M., & Freed, E. O. (2000) · Journal of Virology · doi:10.1128/jvi.74.6.2855-2866.2000 · Cited by 239 · see citing works
“Interestingly, some of these mutations involved basic amino acids within (69) or C terminal to (5) the highly basic domain.”
Background
Efficient HIV‐1 replication can occur in the absence of the viral matrix protein
Reil, H., Bukovsky, A. A., Gelderblom, H. R., & Göttlinger, H. G. (1998) · The EMBO Journal · doi:10.1093/emboj/17.9.2699 · Cited by 241 · see citing works
“Also, relatively small alterations throughout MA which allowed particle formation often prevented virus replication (Yu et al., 1992b; Dorfman et al., 1994; Cannon et al., 1997).”
Background
Human immunodeficiency virus type 1 assembly, release, and maturation
Adamson, C. S., & Freed, E. O. (2007) · Advances in Pharmacology · doi:10.1016/s1054-3589(07)55010-6 · Cited by 179 · see citing works
Opposing Effects of Human Immunodeficiency Virus Type 1 Matrix Mutations Support a Myristyl Switch Model of Gag Membrane Targeting
Paillart, J., & Göttlinger, H. G. (1999) · Journal of Virology · doi:10.1128/jvi.73.4.2604-2612.1999 · Cited by 151 · see citing works
“It is noteworthy in this respect that mutations which affect the globular core of MA often cause indiscriminate assembly both at the plasma membrane and at intracellular membranes (8, 12, 13, 18, 39), a phenotype that might be expected if the myristyl group is constitutively available for membrane binding.”
Background
The Tale of the Long Tail: the Cytoplasmic Domain of HIV-1 gp41
Postler, T. S., & Desrosiers, R. C. (2012) · Journal of Virology · doi:10.1128/jvi.02053-12 · Cited by 122 · see citing works
Prospecting Human Milk Oligosaccharides as a Defense Against Viral Infections
Moore, R. E., Xu, L. L., & Townsend, S. D. (2021) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.0c00807 · Cited by 109 · see citing works
Lentiviral Vectors Encoding Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Receptor Genes Efficiently Convert Peripheral Blood CD8 T Lymphocytes into Cytotoxic T Lymphocytes with Potent In Vitro and In Vivo HIV-1-Specific Inhibitory Activity
Joseph, A., Zheng, J., Follenzi, A., Dilorenzo, T., Sango, K., Hyman, J., Chen, K., Piechocka-Trocha, A., Brander, C., Hooijberg, E., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01812-07 · Cited by 94 · see citing works
“SL9-specific CTLs in particular may have potent anti-HIV activity because the SL9 epitope is efficiently processed and presented by infected cells (6, 25), is derived from a Gag region that must be conserved to maintain viral fitness (6, 9, 25), is independent of T-cell help (36), and is highly recognized by CTLs in g…”
Background
Global Rescue of Defects in HIV-1 Envelope Glycoprotein Incorporation: Implications for Matrix Structure
Tedbury, P. R., Ablan, S. D., & Freed, E. O. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003739 · Cited by 78 · see citing works
Nucleocapsid Promotes Localization of HIV-1 Gag to Uropods That Participate in Virological Synapses between T Cells
Llewellyn, G. N., Hogue, I. B., Grover, J. R., & Ono, A. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001167 · Cited by 85 · see citing works
Trio engagement via plasma membrane phospholipids and the myristoyl moiety governs HIV-1 matrix binding to bilayers
Vlach, J., & Saad, J. S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216655110 · Cited by 75 · see citing works
“Careful analysis of mutants within the PS/PC/PE binding site should be sought because it is likely that substitutions of these highly conserved residues may affect protein stability and thus its function, as was observed for the MA R39E/R43E mutant (60).”
BackgroundInfluential
Detection of a Trimeric Human Immunodeficiency Virus Type 1 Gag Intermediate Is Dependent on Sequences in the Matrix Protein, p17
Morikawa, Y., Zhang, W., HOCKLEY, D. J., Nermut, M. V., & Jones, I. M. (1998) · Journal of Virology · doi:10.1128/jvi.72.9.7659-7663.1998 · Cited by 75 · see citing works
“In this study, however, single-point mutations to alanine at hydrophobic residues Ile60, Pro66, and Leu68 did not prevent particle assembly.”
BackgroundResultInfluentialSelf-citation
Vif and the p55 Gag Polyprotein of Human Immunodeficiency Virus Type 1 Are Present in Colocalizing Membrane-Free Cytoplasmic Complexes
Simon, J. H., Carpenter, E. A., Fouchier, R. A. M., & Malim, M. H. (1999) · Journal of Virology · doi:10.1128/jvi.73.4.2667-2674.1999 · Cited by 62 · see citing works
“It is clear that p55 encodes several important signals (32), with membrane association being directed by a bipartite signal in the p17 (matrix [MA]) component (an amino-terminal myristoyl group and a cluster of positively charged residues) (29, 54, 58, 59) and intermolecular Gag-Gag binding being determined by sequenc…”
Background
Biochemical Characterization of Rous Sarcoma Virus MA Protein Interaction with Membranes
Dalton, A. K., Murray, P. S., Murray, D., & Vogt, V. M. (2005) · Journal of Virology · doi:10.1128/jvi.79.10.6227-6238.2005 · Cited by 65 · see citing works
“A composite homology model for RSV Gag(1-100) was constructed with”
BackgroundMethodInfluential
Identification of a cytoplasmic targeting/retention signal in a retroviral Gag polyprotein
Choi, G., Park, S., Choi, B., Hong, S., Lee, J., Hunter, E., & Rhee, S. S. (1999) · Journal of Virology · doi:10.1128/jvi.73.7.5431-5437.1999 · Cited by 61 · see citing works
“Others have reported that human immunodeficiency virus and Moloney murine leukemia virus (MoMuLV) with amino acid substitutions or deletions in MA undergo capsid assembly within cytoplasmic vacuoles rather than at the plasma membrane (3, 10, 12, 38).”
Retroviral Matrix Proteins: A Structural Perspective
Conte, M. R., & Matthews, S. (1998) · Virology · doi:10.1006/viro.1998.9206 · Cited by 61 · see citing works
“Some evidence for the validity of these models has been provided by mutagenesis studies, in which amino acid changes at the proposed trimer interface of HIV-1 (residues 64, 70, 74) and M-PMV (residues 43, 72) MAs result in inefficient capsid assembly (Cannon et al., 1997; Conte et al., 1997; Morikawa et al., 1995; Rhe…”
BackgroundInfluentialSelf-citation
Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: Structural and mechanistic implications of p17 myristoylation
Wu, Z., Alexandratos, J. N., Ericksen, B., Lubkowski, J. T., Gallo, R. C., & Lu, W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404649101 · Cited by 53 · see citing works
HEED, the Product of the Human Homolog of the Murineeed Gene, Binds to the Matrix Protein of HIV-1
Peytavi, R., Hong, S. S., Gay, B., d’Angeac, A. D., Selig, L., Bénichou, S., Bénarous, R., & Boulanger, P. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.3.1635 · Cited by 49 · see citing works
Antibody Detection by Using a FRET‐Based Protein Conformational Switch
Golynskiy, M. V., Rurup, W. F., & Merkx, M. (2010) · ChemBioChem · doi:10.1002/cbic.201000143 · Cited by 54
Efficient Processing of the Immunodominant, HLA-A*0201-Restricted Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitope despite Multiple Variations in the Epitope Flanking Sequences
Brander, C., Yang, O. O., Jones, N., Lee, Y., Goulder, P., Johnson, R., Trocha, A. K., Colbert, D., Hay, C., Buchbinder, S., et al. (1999) · Journal of Virology · doi:10.1128/jvi.73.12.10191-10198.1999 · Cited by 54 · see citing works
“This region has also been described as important for correct protein folding, p17 trimer complex formation, and viral replication (7).”
Background
RNA Dimerization Defect in a Rous Sarcoma Virus Matrix Mutant
Parent, L. J., Cairns, T. M., Albert, J. A., Wilson, C., Wills, J. W., & Craven, R. C. (2000) · Journal of Virology · doi:10.1128/jvi.74.1.164-172.2000 · Cited by 46 · see citing works
“Genetic analyses of RSV, murine leukemia virus and human immunodeficiency virus (HIV) have revealed many MA mutants that have little or no infectivity, even though particle assembly and budding proceed normally (11, 13, 16, 32, 36, 45, 48, 62).”
Background
The HIV-1 HLA-A2-SLYNTVATL Is a Help-Independent CTL Epitope1
Kan‐Mitchell, J., Bisikirska, B., Wong-Staal, F., Schaubert, K. L., Bajcz, M., & Bereta, M. (2004) · Journal of Immunology · doi:10.4049/jimmunol.172.9.5249 · Cited by 45 · see citing works
“SL9 is also efficiently processed and presented by infected cells (27) and is located in a region of the viral genome that must be conserved to maintain viral fitness (18, 28).”
Background
Understanding retroviral life cycle and its genomic RNA packaging
Chameettachal, A., Mustafa, F., & Rizvi, T. A. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167924 · Cited by 41 · see citing works
D-retrovirus morphogenetic switch driven by the targeting signal accessibility to Tctex-1 of dynein
Vlach, J., Lipov, J., Rumlová, M., Veverka, V., Lang, J., Srb, P., Knejzlík, Z., Pichová, I., Hunter, E., Hrabal, R., et al. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0801765105 · Cited by 40 · see citing works
“Similarly, a substitution of basic for acidic residues in helix A of HIV-1 MA caused relocation of virus assembly to intracellular locations and produced normally budded noninfectious virions (5).”
Background
High-density lipoprotein concentrations relate to the clinical course of HIV viral load in patients undergoing antiretroviral therapy
Alonso‐Villaverde, C., Segués, T., Crespo, B. C., Pérez-Bernalte, R., Rabassa, A., Gomila, M. G., Parra, S., Gozález-Esteban, M. A., Jiménez‐Expósito, M. J., & Masana, L. (2003) · AIDS · doi:10.1097/00002030-200305230-00009 · Cited by 39 · see citing works
“Putative trimer interfaces are created between two polypeptides by packing residues via a series of intermolecular hydrogen bonds [20,34].”
BackgroundInfluential
HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders
Zeinolabediny, Y., Caccuri, F., Colombo, L., Morelli, F., Romeo, M., Rossi, A., Schiarea, S., Ciaramelli, C., Airoldi, C., Weston, R., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10875-0 · Cited by 40 · see citing works
Assembly and Replication of HIV-1 in T Cells with Low Levels of Phosphatidylinositol-(4,5)-Bisphosphate
Monde, K., Chukkapalli, V., & Ono, A. (2011) · Journal of Virology · doi:10.1128/jvi.02266-10 · Cited by 43 · see citing works
“First, although involvement of MA in nuclear import of preintegration complexes is unsubstantiated (reviewed in reference 31), several reports showed that alteration of MA residues modulates other steps of the postentry process (5, 8, 10, 16, 31, 32, 37, 38, 45).”
Background
Mechanisms of PI(4,5)P2 Enrichment in HIV-1 Viral Membranes
Wen, Y., Feigenson, G. W., Vogt, V. M., & Dick, R. A. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.07.018 · Cited by 33 · see citing works
“These amino acids, exposed on the surface of the protein [21,22], interact with negatively charged lipids in the inner leaflet, phosphatidylserine (PS) and PIP2 [9,13,23,24].”
Background
Mutational analysis of the feline immunodeficiency virus matrix protein.
Manrique, M., Celma, C. C. P., González, S., & Affranchino, J. L. (2001) · Virus Research · doi:10.1016/s0168-1702(01)00249-0 · Cited by 34
Reversion of a Human Immunodeficiency Virus Type 1 Matrix Mutation Affecting Gag Membrane Binding, Endogenous Reverse Transcriptase Activity, and Virus Infectivity
Kiernan, R. E., Ono, A., & Freed, E. O. (1999) · Journal of Virology · doi:10.1128/jvi.73.6.4728-4737.1999 · Cited by 30 · see citing works
“An assemblyrelease defect associated with the 73EK substitution is consistent with a previous report that described reduced virus production with a 69TE/73EK double mutant (5), and an association between trimer interface mutations and virus assembly defects has been reported (36).”
Characterization of Mother-Infant HIV Type 1 gag p17 Sequences Associated with Perinatal Transmission
Hahn, T., Matala, E., Chappey, C., & Ahmad, N. (1999) · AIDS Research and Human Retroviruses · doi:10.1089/088922299310584 · Cited by 31 · see citing works
“We then examined the three classes of mutants in our 166 p17 sequences as described previously, 68 including proteins containing substitutions at internal residues that grossly distorted the structure and particle formation, mutations at trimer interfaces that allowed correct folding but defects in…”
Influential
Calmodulin and HIV Type 1: Interactions with Gag and Gag Products
Radding, W., Williams, J. P., McKenna, M. A., Tummala, R., Hunter, E., Tytler, E. M., & McDonald, J. M. (2000) · AIDS Research and Human Retroviruses · doi:10.1089/088922200750006047 · Cited by 33 · see citing works
“20 Again assuming MLCK peptide-like binding, R43 in particular would be in a position to provide positive charge likely to be important for calmodulin binding, and the mutation to negative charge would be expected to diminish such binding significantly.”
A Highly Conserved Residue in the C-Terminal Helix of HIV-1 Matrix Is Required for Envelope Incorporation into Virus Particles
Brandano, L. A., & Stevenson, M. (2011) · Journal of Virology · doi:10.1128/jvi.06047-11 · Cited by 30 · see citing works
“3, has close proximity to glutamate 99, as well as to a C-terminal hydrophobic pocket described previously (7).”
BackgroundInfluential
Degeneracy and Repertoire of the Human HIV-1 Gag p1777–85 CTL Response1
Kan‐Mitchell, J., Bajcz, M., Schaubert, K. L., Price, D., Brenchley, J., Asher, T. E., Douek, D., Ng, H. L., Yang, O. O., Rinaldo, C., et al. (2006) · Journal of Immunology · doi:10.4049/jimmunol.176.11.6690 · Cited by 28
“In patients, SL9-CTLs have been detected in GALT (21, 29), suggesting that these cells may also be active in mucosal responses.”
Background
Human immunodeficiency virus type 1 KK26-27 matrix mutants display impaired infectivity, circularization and integration but not nuclear import.
Mannioui, A., Nelson, E., Schiffer, C., Felix, N., le Rouzic, E., Bénichou, S., Gluckman, J., & Canque, B. (2005) · Virology · doi:10.1016/j.virol.2005.05.023 · Cited by 28
“In this respect, onemust keep inmind that, beside its pivotal function in the assembly and budding of viral particles, MA also plays an important role at early stages of the virus cycle, conditioning its infectivity, uncoating and reverse transcription (Bukrinskaya et al., 1998; Cannon et al., 1997; Casella et al., 19…”
Background
The molecular basis of HIV capsid assembly
Jones, I. M., & Morikawa, Y. (1998) · Reviews in Medical Virology · doi:10.1002/(sici)1099-1654(199804/06)8:2 · Cited by 24 · see citing works
HIV-1 p17 Matrix Protein Interacts with Heparan Sulfate Side Chain of CD44v3, Syndecan-2, and Syndecan-4 Proteoglycans Expressed on Human Activated CD4+ T Cells Affecting Tumor Necrosis Factor α and Interleukin 2 Production
Francesco, M. A. D., Baronio, M., & Poiesi, C. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.191270 · Cited by 21 · see citing works
Emerging Roles of Heparan Sulfate Proteoglycans in Viral Pathogenesis
Koganti, R., Memon, A., & Shukla, D. (2021) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0041-1725068 · Cited by 24 · see citing works
A Single-Nucleotide Synonymous Mutation in the gag Gene Controlling Human Immunodeficiency Virus Type 1 Virion Production
Hamano, T., Matsuo, K., Hibi, Y., Victoriano, A., Takahashi, N., Mabuchi, Y., Soji, T., Irie, S., Sawanpanyalert, P., Yanai, H., et al. (2006) · Journal of Virology · doi:10.1128/jvi.01596-06 · Cited by 22
Molecular Interaction Studies of HIV-1 Matrix Protein p17 and Heparin
Bugatti, A., Giagulli, C., Urbinati, C., Caccuri, F., Chiodelli, P., Oreste, P., Fiorentini, S., Orro, A., Milanesi, L., D’Ursi, P., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.400077 · Cited by 31 · see citing works
“The matrix protein p17 plays important roles in HIV-1 life cycle (1) regulating both early and late stages of viral replication such as P55GAG transport to the membrane (2) and envelope glycoproteins incorporation into nascent virions (3).”
Background
Functional relationship between the matrix proteins of feline and simian immunodeficiency viruses
Manrique, M. L., González, S. A., & Affranchino, J. L. (2004) · Virology · doi:10.1016/j.virol.2004.07.029 · Cited by 18 · see citing works
Heparin and heparan sulfate proteoglycans promote HIV-1 p17 matrix protein oligomerization: computational, biochemical and biological implications
Bugatti, A., Paiardi, G., Urbinati, C., Chiodelli, P., Orro, A., Uggeri, M., Milanesi, L., Caruso, A., Caccuri, F., D’Ursi, P., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-52201-w · Cited by 21 · see citing works
Viral fitness implications of variation within an immunodominant CD8+ T-cell epitope of HIV-1.
Christie, N., Willer, D., Lobritz, M., Chan, J., Arts, E., Ostrowski, M., Cochrane, A., Luscher, M., & MacDonald, K. (2009) · Virology · doi:10.1016/j.virol.2009.03.003 · Cited by 18
“Although this epitope is located in p17 subunit of Gag, rather than the more conserved p24, the importance of p17 during viral entry, nuclear import of HIV DNA and late infection has been clearly demonstrated (Cannon et al., 1997; Freed et al., 1994; Ono et al., 2000).”
Background
Inhibition of viral assembly in murine cells by HIV-1 matrix.
Hübner, W., & Chen, B. K. (2006) · Virology · doi:10.1016/j.virol.2006.04.024 · Cited by 18 · see citing works
“Mutations in HIV-1 MA or total replacement of MA with a constitutive membrane anchor results in increased assembly at inappropriate intracellular compartments (Cannon et al., 1997; Facke et al., 1993; Lee and Linial, 1994; Ono and Freed, 2004; Ono et al., 2000; Reil et al., 1998; Spearman et al., 1994; Yuan et al., 19…”
Background
Conjugation of cell-penetrating peptides leads to identification of anti-HIV peptides from matrix proteins
Narumi, T., Komoriya, M., Hashimoto, C., Wu, H., Nomura, W., Suzuki, S., Tanaka, T., Chiba, J., Yamamoto, N., Murakami, T., et al. (2012) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.12.055 · Cited by 19 · see citing works
A comparative analysis of viral matrix proteins using disorder predictors
Goh, G. K., Dunker, A. K., & Uversky, V. N. (2008) · Virology Journal · doi:10.1186/1743-422x-5-126 · Cited by 63 · see citing works
“The viral matrix protein underlies the envelope of a virion, representing essentially a link between the envelope and the nucleocapsid [1,2].”
Background
Evolution of feline immunodeficiency virus Gag proteins
Burkala, E. J., & Poss, M. L. (2007) · Virus Genes · doi:10.1007/s11262-006-0058-8 · Cited by 13 · see citing works
Role of the long cytoplasmic domain of the SIV Env glycoprotein in early and late stages of infection
Vzorov, A., Weidmann, A., Kozyr, N., Khaoustov, V., Yoffe, B., & Compans, R. (2007) · Retrovirology · doi:10.1186/1742-4690-4-94 · Cited by 14 · see citing works
Development of anti‐HIV peptides based on a viral capsid protein
Mizuguchi, T., Ohashi, N., Matsumoto, D., Hashimoto, C., Nomura, W., Yamamoto, N., Murakami, T., & Tamamura, H. (2017) · Biopolymers · doi:10.1002/bip.22920 · Cited by 13
Small-Molecule Anti-HIV-1 Agents Based on HIV-1 Capsid Proteins
Kobayakawa, T., Yokoyama, M., Tsuji, K., Fujino, M., Kurakami, M., Boku, S., Nakayama, M., Kaneko, M., Ohashi, N., Kotani, O., et al. (2021) · Biomolecules · doi:10.3390/biom11020208 · Cited by 12
Anti-HIV screening for cell-penetrating peptides using chloroquine and identification of anti-HIV peptides derived from matrix proteins
Mizuguchi, T., Ohashi, N., Nomura, W., Komoriya, M., Hashimoto, C., Yamamoto, N., Murakami, T., & Tamamura, H. (2015) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2015.06.020 · Cited by 12 · see citing works
Gag-derived proteins of HIV-1 isolates from Indian patients: cloning, expression, and purification of p17 of B- and C-subtypes.
Gupta, S., Arora, K., Gupta, A., & Chaudhary, V. (2001) · Protein Expression and Purification · doi:10.1006/prep.2001.1389 · Cited by 9 · see citing works
NMR Studies of Retroviral Genome Packaging
Boyd, P. S., Brown, J. B., Brown, J. D., Catazaro, J., Chaudry, I., Ding, P., Dong, X., Marchant, J., O’Hern, C., Singh, K., et al. (2020) · Viruses · doi:10.3390/v12101115 · Cited by 9 · see citing works
“NMR was also used to characterize and explain the action of several MA point mutations that inhibit plasma membrane targeting by disruption of the tertiary structure [148], stabilization of the myr-sequestered conformation [120,122], or through removal of basic residues important for both PI(4,5)P2 discrimination and…”
Method
Exploratory studies on CA-15L, an anti-HIV active HIV-1 capsid fragment.
Tsuji, K., Owusu, K., Kobayakawa, T., Wang, R.-Y., Fujino, M., Kaneko, M., Yamamoto, N., Murakami, T., & Tamamura, H. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115488 · Cited by 7
Probing the interactions of the HIV-1 matrix protein-derived polybasic region with lipid bilayers: insights from AFM imaging and force spectroscopy
Aryal, C. M., & Pan, J. (2024) · European Biophysics Journal · doi:10.1007/s00249-023-01697-2 · Cited by 6 · see citing works
“The highly basic region, characterized by a dense clus - ter of positively charged amino acid residues, represents the second domain regulating MA’s membrane binding (Facke et al. 1993; Cannon et al. 1997; Ono et al. 2000; Hermida-Matsumoto and Resh 2000).”
Emergence of a Three Codon Deletion in gag p17 in HIV Type 1 Subtype C Long-Term Survivors, and General Population Spread
McCormack, G. P., Glynn, J., Clewley, J., Crampin, A., Travers, S. A. A., Redmond, N., Keane, T., Sibande, F., Mulawa, D., & Fine, P. (2006) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2006.22.195 · Cited by 6
Low-molecular-weight anti-HIV-1 agents targeting HIV-1 capsid proteins
Kobayakawa, T., Yokoyama, M., Tsuji, K., Fujino, M., Kurakami, M., Onishi, T., Boku, S., Ishii, T., Miura, Y., Shinohara, K., et al. (2023) · RSC Advances · doi:10.1039/d2ra06837k · Cited by 5
Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“Along the same lines, alterations in the MA domain of HIV-1 Gag, whether through amino acid substitutions or deletions, have been shown to redirect virus assembly to the cyto-plasm or intracellular membranes, such as the endoplasmic reticulum (Fäcke et al. 1993 , Cannon et al. 1997 ).”
Discovery of Dehydroamino Acid Residues in the Capsid and Matrix Structural Proteins of HIV-1
Miller, R., Knoener, R. A., Benner, B. E., Frey, B. L., Scalf, M., Shortreed, M. R., Sherer, N. M., & Smith, L. M. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00867 · Cited by 5 · see citing works
Potent leads based on CA-19L, an anti-HIV active HIV-1 capsid fragment.
Tsuji, K., Wang, R.-Y., Kobayakawa, T., Owusu, K., Fujino, M., Kaneko, M., Yamamoto, N., Murakami, T., & Tamamura, H. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115923 · Cited by 4
The central domain of the matrix protein of HIV-1: influence on protein structure and virus infectivity
Ellenrieder, A.-D., Kremer, W., Kattenbeck, B., Hantschel, O. D., Horn, G., Kalbitzer, H. R., & Modrow, S. (2004) · Biological Chemistry · doi:10.1515/bc.2004.026 · Cited by 4 · see citing works
Molecular Characterization of Porcine Endogenous Retrovirus gag Genes from Pigs in Korea
Lee, J., Lee, D., Yoo, J., Kim, G.-W., Park, H.-Y., Lee, H.-T., & Kim, Y. B. (2006) · Journal of Bacteriology and Virology · doi:10.4167/jbv.2006.36.3.185 · Cited by 3 · see citing works
Effects of mutations in an HIV‐1 gag gene containing a 107‐codon tandem repeat in the matrix region on assembly and processing of the protein product
Liao, W., Chiu, H.-C., & Wang, C.-T. (2004) · Journal of Medical Virology · doi:10.1002/jmv.20209 · Cited by 2 · see citing works
“This is in contrast to a previous study showing that the double substitution mutation (T70E/E74K) could significantly affect virus particle production [Cannon et al., 1997].”
BackgroundResult
Detection of reverse transcriptase activity in the serum of patients with motor neurone disease
Andrews, W. D., Tuke, P. W., Al‐Chalabi, A., Gaudin, P., Ijaz, S., Parton, M. J., & Garson, J. A. (2000) · Journal of Medical Virology · doi:10.1002/1096-9071(200008)61:4 · Cited by 67 · see citing works
RNA ‐centric world of retroviruses: unravelling the molecular strategies of genomic RNA packaging
Jehad, M. A., Prabhu, S., Ali, L. M., Pillai, V. N., Mustafa, F., & Rizvi, T. A. (2026) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1002/brv.70188 · Cited by 2 · see citing works
Identification of The Potential Matrix Protein of Invertebrate Iridescent Virus 6 (IIV6).
Gencer, D., Yeşilyurt, A., Ozsahin, E., Muratoğlu, H., Yazici, Z. A., Demırbag, Z., & Nalçacıoğlu, R. (2023) · Journal of Invertebrate Pathology · doi:10.1016/j.jip.2023.107885 · Cited by 2
Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR
Konagaya, Y., Miyakawa, R., Sato, M., Matsugami, A., Watanabe, S., Hayashi, F., Kigawa, T., & Nishimura, C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167176 · Cited by 2 · see citing works
Slight difference in primary amino acid sequence of p17 matrix protein of HIV-1 exerts profound influence on its antigenicity
Taniguchi, K., Tsuchie, H., Kageyama, S., Iwasaki, M., Takagi, T., Sasao, F., Ueda, S., & Kurimura, T. (1998) · Archives of Virology · doi:10.1007/s007050050339 · Cited by 2 · see citing works
“[33] reported that the helical structure corresponding to the recognition site of A144 was important to the biological function of p17.”
Background
Anti-P30-52 Monoclonal Antibody Cross-Reacted to Env V3 and Inhibited the Viral Multiplication of HIV-1-Infected MT-4 Cells
Ota, A., BAUTISTA, A. N., YADAV, M. L., & Ueda, S. (1999) · Hybridoma · doi:10.1089/hyb.1999.18.139 · Cited by 1 · see citing works
Identifying Conserved Regions in HIV-1 Proteins by Entropy Analysis of Sequence Variability
Shchemelev, A., Serikova, E., Ostankova, Y., Davydenko, V. S., Ramsay, E., & Totolian, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27115139
“A 1997 study described the role of this helix in the interaction of p17 with the cell membrane and noted that virions with mutations in this region lacked infectious activity [17].”
Identification of peptide-based hepatitis B virus capsid inhibitors based on the viral core protein.
Fujimoto, J., Kawahara, K., Takeda, K., Takeo, S., Sato, K., Nakashima, K., Mase, N., Yokoyama, M., Suzuki, T., & Narumi, T. (2024) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2024.130054
Structural Disorder in Matrix Proteins of HIV‐Related Viruses
Goh, G. K., Xue, B., Dunker, A. K., & Uversky, V. N. (2011) · Wiley eBooks · doi:10.1002/9781118135570.ch6
Conjugated Compounds Involving Peptides
Tamamura, H., Kobayakawa, T., & Ohashi, N. (2018) · SpringerBriefs in pharmaceutical science & drug development · doi:10.1007/978-981-10-7691-6_6
Investigation of the C-Terminal Helix of HIV-1 Matrix: A Region Essential for Multiple Functions in the Viral Life Cycle: A Dissertation
Brandano, L. A. (2011) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/5zmj-9x81

Authors: Cannon, P. M., Matthews, S., Clark, N., Byles, E. D., Iourin, O., Hockley, D. J., Kingsman, S. M., & Kingsman, A. J.
Affiliations: University of Oxford (GB)
ORCID: Cannon, P M
Matthews, S
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 1997-05
Volume: 71
Issue: 5
Pages: 3474-3483
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.71.5.3474-3483.1997
PMC: PMC191494
OpenAlex: W2104395143
Cited by: 86
References: 0
Citations by year: 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 3 · 2012: 6
FWCI: 1.83
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Biotechnology and Biological Sciences Research Council (SBD07462)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords: HIV-1, structure-function relationship, rational mutagenesis, viral assembly, protein folding, viral budding
MeSH terms: Amino Acid Sequence, Humans, Molecular Sequence Data, Mutation, Structure-Activity Relationship, Viral Proteins, Virion, Virus Replication, HIV Antigens, HIV-1, Gene Products, gag, HIV Long Terminal Repeat, gag Gene Products, Human Immunodeficiency Virus

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Structure-function studies of the human immunodeficiency virus type 1 matrix protein, p17

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Record

About these checks