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.

Scientific Reports
|March 28, 2017
PubMed

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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