(P19) Biological characteristics of Transmitted founder HIV-1 viruses: sensitivity to Interferon alpha, replication kinetics and virus production
Ashokkumar Manickam 1,2*, Aanand Sonawanne 1, Maike Sperk 2, Srikanth P Tripathy 1, Ujjwal Neogi 2,3 and Luke Elizabeth Hanna 1*.
1Department of HIV/AIDS, National Institute for Research in Tuberculosis, Chennai, India. 2Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. 3Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA. *Correspondence
Background: Type I interferons, particularly interferon alpha (IFN-α), play a vital role in the host’s anti-viral defense, protecting immune cells from infection by interfering with viral replication. However, the clever virus utilizes superior and more rapidly evolving strategies and capably exploits the IFN-α response for its replication, spread, and pathogenic function. Previous knowledge informs us that the viral isolates in recent heterosexual infection have varying fitness and respond differently to the host immune response, and thus succeed in establishing infection in the human host.
Methods: In this study, we attempted to determine the biological characteristics of infectious transmitted founder (TF) viruses (n=8) and non-transmitted (NT) viruses (n=8) derived from infants infected with HIV-1 through the vertical route in terms of susceptibility/resistance to IFN-, replication fitness and viral productivity in PHA-stimulated primary CD4+ T cells over a short span of time.
Results: The in vitro studies demonstrated that TF viruses were resistant to IFN-α during the very near moment of transmission, but in the subsequent time points, they became susceptible to IFN-α. We did not observe much of a difference in the replicative fitness of the TF viruses in cultures treated with and without IFN-α, but the difference was statistically significant in the case of NT viruses obtained from the same individual.
Conclusion: Despite increased susceptibility to IFN-α, NT viruses produced more cell-free viral particles than the TF viruses. Similar results were also obtained in cultures treated with an entry inhibitor, maroviroc (MVC). Thus, the study identified some interesting characteristics that are unique to TF viruses and prompt further investigation into virus-host interaction during the early stages of HIV infection.