OBJECTIVE: To examine the relationship between infectivity of HIV-1 variants in dendritic cell (DC)-mediated in trans infection of T cells and plasma viral RNA levels in infected subjects. METHODS: HIV-1 was isolated from peripheral blood mononuclear cells of chronically infected individuals, typed for coreceptor usage, and viral replication were examined in monocyte-derived DCs-peripheral blood lymphocytes cocultures. The rate of p24 antigen production during the logarithmic phase of viral replication was determined by enzyme-linked immunosorbent assay. Additionally, nef variants were cloned and expressed in trans with a HIV luciferase vector and CCR5-tropic HIV-1 envelope, and infectivity was measured in DC-mediated capture-transfer assays. RESULTS: Replication capacity of HIV-1 viral CCR5-tropic isolates in monocyte-derived dendritic cells-peripheral blood lymphocytes cocultures was linearly associated with the plasma viral RNA levels in a cohort of HIV-1-infected individuals exhibiting an inverse relationship between plasma viral RNA and CD4 cell count. Furthermore, infectivity activity of nef variants in context of DC-mediated enhanced infection of T cells also showed a linear relationship to plasma viral RNA levels. CONCLUSIONS: These results illustrate that replication capacity of HIV-1 in DC T-cell cultures is a significant determinant of plasma viral RNA level. The data suggest that adaptation of HIV-1 to DC interactions with T cells influences the level of viral replication in the host.
OBJECTIVE: To examine the relationship between infectivity of HIV-1 variants in dendritic cell (DC)-mediated in trans infection of T cells and plasma viral RNA levels in infected subjects. METHODS:HIV-1 was isolated from peripheral blood mononuclear cells of chronically infected individuals, typed for coreceptor usage, and viral replication were examined in monocyte-derived DCs-peripheral blood lymphocytes cocultures. The rate of p24 antigen production during the logarithmic phase of viral replication was determined by enzyme-linked immunosorbent assay. Additionally, nef variants were cloned and expressed in trans with a HIV luciferase vector and CCR5-tropic HIV-1 envelope, and infectivity was measured in DC-mediated capture-transfer assays. RESULTS: Replication capacity of HIV-1 viral CCR5-tropic isolates in monocyte-derived dendritic cells-peripheral blood lymphocytes cocultures was linearly associated with the plasma viral RNA levels in a cohort of HIV-1-infected individuals exhibiting an inverse relationship between plasma viral RNA and CD4 cell count. Furthermore, infectivity activity of nef variants in context of DC-mediated enhanced infection of T cells also showed a linear relationship to plasma viral RNA levels. CONCLUSIONS: These results illustrate that replication capacity of HIV-1 in DC T-cell cultures is a significant determinant of plasma viral RNA level. The data suggest that adaptation of HIV-1 to DC interactions with T cells influences the level of viral replication in the host.
Authors: David McDonald; Li Wu; Stacy M Bohks; Vineet N KewalRamani; Derya Unutmaz; Thomas J Hope Journal: Science Date: 2003-05-01 Impact factor: 47.728
Authors: Monica T Yu Kimata; Marina Cella; Julia E Biggins; Colin Rorex; Robert White; Sarah Hicks; Joelle M Wilson; Parul G Patel; Jonathan S Allan; Marco Colonna; Jason T Kimata Journal: J Virol Date: 2002-12 Impact factor: 5.103
Authors: S Pöhlmann; F Baribaud; B Lee; G J Leslie; M D Sanchez; K Hiebenthal-Millow; J Münch; F Kirchhoff; R W Doms Journal: J Virol Date: 2001-05 Impact factor: 5.103
Authors: Rajesh Thippeshappa; Patricia Polacino; Monica T Yu Kimata; Edward B Siwak; David Anderson; Weiming Wang; Laura Sherwood; Reetakshi Arora; Michael Wen; Paul Zhou; Shiu-Lok Hu; Jason T Kimata Journal: J Virol Date: 2011-02-02 Impact factor: 5.103