title: A Cell Internalizing Antibody Targeting Capsid Protein (p24) Inhibits the Replication of HIV-1 in T Cells Lines and PBMCs: A Proof of Concept Study.
abstract: There remains a need for newer therapeutic approaches to combat HIV/AIDS. Viral capsid protein p24 plays important roles in HIV pathogenesis. Peptides and small molecule inhibitors targeting p24 have shown to inhibit virus replication in treated cell. High specificity and biological stability of monoclonal antibodies (mAbs) make them an attractive contender for in vivo treatments. However, mAbs do not enter into cells, thus are restricted to target surface molecules. This also makes targeting intracellular HIV-1 p24 a challenge. A mAb specific to p24 that can internalize into the HIV-infected cells is hypothesized to inhibit the virus replication. We selected a mAb that has previously shown to inhibit p24 polymerization in an in vitro assay and chemically conjugated it with cell penetrating peptides (CPP) to generate cell internalizing anti-p24 mAbs. Out of 8 CPPs tested, κFGF-MTS -conjugated mAbs internalized T cells most efficiently. At nontoxic concentration, the κFGF-MTS-anti-p24-mAbs reduced the HIV-1 replication up to 73 and 49% in T-lymphocyte and PBMCs respectively. Marked inhibition of HIV-1 replication in relevant cells by κFGF-MTS-anti-p24-mAbs represents a viable strategy to target HIV proteins present inside the cells.
authors.affiliation: Oncological and Radiological Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Kepala Batas, Pulau Pinang, Malaysia.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ali
authors.affiliation: Oncological and Radiological Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Kepala Batas, Pulau Pinang, Malaysia.
authors.forename: Sin-Yeang
authors.initials: SY
authors.lastname: Teow
authors.affiliation: Oncological and Radiological Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Kepala Batas, Pulau Pinang, Malaysia.
authors.forename: Tasyriq Che
authors.initials: TC
authors.lastname: Omar
authors.affiliation: Institute for Medical Research, Jalan Pahang, 50588, Kuala Lumpur, Malaysia.
authors.forename: Alan Soo-Beng
authors.initials: AS
authors.lastname: Khoo
authors.affiliation: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Pulau Pinang, Malaysia.
authors.forename: Tan Soo
authors.initials: TS
authors.lastname: Choon
authors.affiliation: Regenerative Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Kepala Batas, Pulau Pinang, Malaysia.
authors.forename: Narazah Mohd
authors.initials: NM
authors.lastname: Yusoff
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D001692:Biological Transport; D002213:Capsid / Q000737:chemistry / Q000276:immunology; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D061251:Primary Cell Culture; D021381:Protein Transport; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D057846:Cell-Penetrating Peptides; D016655:HIV Core Protein p24; D007074:Immunoglobulin G