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Nucleocapsid Annealing-Mediated Electrophoresis NAME Assay Allows the Rapid Identification of HIV-1 Nucleocapsid Inhibitors
Published on: January 19, 2015
Cyclophilins and nucleoporins are required for infection mediated by capsids from circulating HIV-2 primary isolates
João I Mamede1, Florence Damond2, Ariel de Bernardo1
1Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, 1919 route de Mende, 34293 Montpellier cedex 5, France; Université de Montpellier, 163 rue Auguste Broussonnet, 34090 Montpellier, France.
Abstract:
HIV-2 groups have emerged from sooty mangabey SIV and entered the human population in Africa on several separate occasions. Compared to world pandemic HIV-1 that arose from the chimpanzee SIVcpz virus, the SIVsm-derived HIV-2, largely confined to West Africa, is less replicative, less transmissible and less pathogenic. Here, we evaluated the interactions between host cellular factors, which control HIV-1 infection and target the capsid, and HIV-2 capsids obtained from primary isolates from patients with different disease progression status. We showed that, like HIV-1, all HIV-2 CA we tested exhibited a dependence on cyclophilin A. However, we observed no correlation between HIV-2 viremia and susceptibility to hu-TRIM5alpha or dependence to CypA. Finally, we found that all CA from HIV-2 primary isolates exploit Nup358 and Nup153 for nucleus transposition. Altogether, these findings indicate that the ability to use the two latter nucleoporins is essential to infection of human cells for both HIV-1 and HIV-2. This dependence provides another molecular target that could be used for antiviral strategies against both HIV-1 and 2, based on both nucleoporins.
Insights
Human immunodeficiency virus type 2 (HIV-2) relies on host factors like cyclophilin A and specific nucleoporins (Nup358, Nup153) for infection, similar to HIV-1. These shared dependencies offer potential targets for developing new antiviral strategies against both HIV types.
Area of Science:
- Virology and Immunology
- Molecular Biology
- Infectious Diseases
Background:
- Human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV-1 and primarily circulates in West Africa.
- Understanding host-pathogen interactions is crucial for developing effective antiviral therapies.
- HIV-1 infection relies on host cellular factors, including cyclophilin A (CypA) and nucleoporins, for replication.
Purpose of the Study:
- To investigate the interactions between HIV-2 capsids and host cellular factors involved in HIV-1 infection.
- To compare the dependence of HIV-2 on cyclophilin A and TRIM5alpha with that of HIV-1.
- To determine the role of nucleoporins Nup358 and Nup153 in HIV-2 nuclear import.
Main Methods:
- Analysis of HIV-2 capsid (CA) interactions with host factors using primary isolates from patients.
- Assessment of HIV-2 dependence on cyclophilin A (CypA) and susceptibility to hu-TRIM5alpha.
- Evaluation of HIV-2 CA's exploitation of Nup358 and Nup153 for nuclear transposition.
Main Results:
- All tested HIV-2 CA displayed a dependence on cyclophilin A, mirroring HIV-1.
- No correlation was found between HIV-2 viremia and susceptibility to hu-TRIM5alpha or CypA dependence.
- All HIV-2 primary isolates utilized Nup358 and Nup153 for nuclear import.
Conclusions:
- The ability to utilize Nup358 and Nup153 is essential for HIV-2 infection of human cells, similar to HIV-1.
- Host nucleoporins represent a conserved molecular target for antiviral strategies against both HIV-1 and HIV-2.
- Further research into these host-pathogen interactions could lead to novel therapeutic interventions.
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