Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies
To prevent the spread of HIV-1, a vaccine should elicit antibodies that block viral entry for all cell types. Recently, we have developed a virus capture assay to quantitatively examine early time points of infection. Here we present data on the ability of bNAbs to inhibit capture (1 h) or replicati...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/8/4/782 |
| _version_ | 1797544038130253824 |
|---|---|
| author | Jiae Kim Venigalla B. Rao Mangala Rao |
| author_facet | Jiae Kim Venigalla B. Rao Mangala Rao |
| author_sort | Jiae Kim |
| collection | DOAJ |
| description | To prevent the spread of HIV-1, a vaccine should elicit antibodies that block viral entry for all cell types. Recently, we have developed a virus capture assay to quantitatively examine early time points of infection. Here we present data on the ability of bNAbs to inhibit capture (1 h) or replication (48 h) of purified primary acute or chronic HIV or infectious molecular clones (IMCs) in human peripheral blood mononuclear cells (PBMCs) as quantified by qRT-PCR. Although bNAbs significantly inhibited HIV-1 replication in PBMCs in a virus subtype and in a PBMC-donor specific manner, they did not inhibit virus capture of primary viruses. In contrast, IMC capture and replication in PBMCs and purified CD4<sup>+</sup> T cells were significantly inhibited by bNAbs, thus indicating that unlike IMCs, primary HIV-1 may initially bind to other cell surface molecules, which leads to virus capture even in the presence of bNAbs. Our results demonstrate that the initial interactions and some aspects of infectivity of primary HIV-1 and IMCs are inherently different, which underscores the importance of studying virus transmission using primary viruses in <i>in vitro</i> studies, an issue that could impact HIV-1 vaccine design strategies. |
| first_indexed | 2024-03-10T13:54:47Z |
| format | Article |
| id | doaj.art-fbfd6431c30d423982f58012033d9b54 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T13:54:47Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-fbfd6431c30d423982f58012033d9b542023-11-21T01:48:57ZengMDPI AGVaccines2076-393X2020-12-018478210.3390/vaccines8040782Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing AntibodiesJiae Kim0Venigalla B. Rao1Mangala Rao2US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USADepartment of Biology, The Catholic University of America, 620 Michigan Avenue NE, Washington, DC 20064, USALaboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USATo prevent the spread of HIV-1, a vaccine should elicit antibodies that block viral entry for all cell types. Recently, we have developed a virus capture assay to quantitatively examine early time points of infection. Here we present data on the ability of bNAbs to inhibit capture (1 h) or replication (48 h) of purified primary acute or chronic HIV or infectious molecular clones (IMCs) in human peripheral blood mononuclear cells (PBMCs) as quantified by qRT-PCR. Although bNAbs significantly inhibited HIV-1 replication in PBMCs in a virus subtype and in a PBMC-donor specific manner, they did not inhibit virus capture of primary viruses. In contrast, IMC capture and replication in PBMCs and purified CD4<sup>+</sup> T cells were significantly inhibited by bNAbs, thus indicating that unlike IMCs, primary HIV-1 may initially bind to other cell surface molecules, which leads to virus capture even in the presence of bNAbs. Our results demonstrate that the initial interactions and some aspects of infectivity of primary HIV-1 and IMCs are inherently different, which underscores the importance of studying virus transmission using primary viruses in <i>in vitro</i> studies, an issue that could impact HIV-1 vaccine design strategies.https://www.mdpi.com/2076-393X/8/4/782HIV-1virus capturebroadly neutralizing antibodiesprimary virusesinfectious molecular clonesPBMCs |
| spellingShingle | Jiae Kim Venigalla B. Rao Mangala Rao Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies Vaccines HIV-1 virus capture broadly neutralizing antibodies primary viruses infectious molecular clones PBMCs |
| title | Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies |
| title_full | Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies |
| title_fullStr | Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies |
| title_full_unstemmed | Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies |
| title_short | Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies |
| title_sort | primary hiv 1 and infectious molecular clones are differentially susceptible to broadly neutralizing antibodies |
| topic | HIV-1 virus capture broadly neutralizing antibodies primary viruses infectious molecular clones PBMCs |
| url | https://www.mdpi.com/2076-393X/8/4/782 |
| work_keys_str_mv | AT jiaekim primaryhiv1andinfectiousmolecularclonesaredifferentiallysusceptibletobroadlyneutralizingantibodies AT venigallabrao primaryhiv1andinfectiousmolecularclonesaredifferentiallysusceptibletobroadlyneutralizingantibodies AT mangalarao primaryhiv1andinfectiousmolecularclonesaredifferentiallysusceptibletobroadlyneutralizingantibodies |