The increased replicative capacity of a late-stage simian immunodeficiency virus mne variant is evident in macrophage- or dendritic cell-T-cell cocultures.
Human and simian immunodeficiency virus (HIV and SIV) may co-opt antigen capture and presentation functions of antigen presenting cells (APCs) to facilitate infection of CD4+ T-cells. To address whether the replicative capacity of SIV in the host may be associated with the extent of viral replication in response to APC-T-cell interactions, we compared the replicative phenotypes of cloned early and late-stage SIVmne variants of known pathogenicity. Here, we show that the highly pathogenic late variant SIVmne027 replicates more efficiently in both macrophage- and dendritic cell (DC)-T-cell cocultures than the minimally pathogenic early virus SIVmneCl8. Contact between either macrophages or DC and T-cells increases replication of SIVmne027. Our analysis also demonstrates that mutations in pol and nef contribute to the greater replicative capacity of SIVmne027 in DC- or macrophage-T-cell cocultures. Together, these data suggest that variant viruses that evolve to replicate vigorously in response to APC-T-cell interactions may have increased replicative capacity in vivo.
Kimata
Jason T
JT
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Wilson
Joelle M
JM
Patel
Parul G
PG
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000502:physiology / Q000821:virology*; D014644:Genetic Variation; D008254:Macaca nemestrina; D008264:Macrophages / Q000502:physiology / Q000821:virology*; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D014779:Virus Replication