Tropism demonstrates affinity, yes or no. RO is q
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Posted On: 04/21/2021 7:07:17 PM
Tropism demonstrates affinity, yes or no. RO is quantitative and would be used for dosing.
Tropism and Coreceptor Use
Tropism is an important determinant of HIV pathogenesis and persistence of infection in the periphery and the CNS. Viral tropism refers to the type of cell in which infection is established. HIV strains are classified as macrophage (M) tropic, T-cell (T) tropic, or dual tropic. Viral coreceptor utilization affects but does not entirely determine tropism. In general, M-tropic HIV preferentially uses CCR5 as a coreceptor (R5 virus), while T-tropic HIV-1 preferentially uses CXCR4 (X4 virus). Dual tropic HIV-1 is capable of using either CXCR4 or CCR5.3 However, since both macrophages and T cells are capable of expressing CCR5 and CXCR4, and each cell type is capable of supporting infection by either strain of virus, coreceptor use and tropism can be discordant. Often, there is a transition during infection from R5 to X4 tropism. R5 virus initially infects mucosal dendritic cells and macrophages, and memory CD4 T cells that express CCR5, especially in the gut-associated lymphoid tissue (GALT), are subsequently infected. Macrophages and T cells harboring R5 HIV disseminate and establish reservoirs in various compartments (see Gorry and Ancuta3 for a review of viral reservoirs). X4 tropic HIV typically arises later in infection and is associated with a rapid decline in CD4 T cells, CD8 cell apoptosis, and an impaired humoral response, suggesting a link between the emergence of X4 tropic virus, clinical deterioration, and progression to AIDS. However, since HIV continues to mutate during the entire course of infection, individual infections can end up advancing to any permutation of X4, R5, or dual tropic virus.
Tropism and Coreceptor Use
Tropism is an important determinant of HIV pathogenesis and persistence of infection in the periphery and the CNS. Viral tropism refers to the type of cell in which infection is established. HIV strains are classified as macrophage (M) tropic, T-cell (T) tropic, or dual tropic. Viral coreceptor utilization affects but does not entirely determine tropism. In general, M-tropic HIV preferentially uses CCR5 as a coreceptor (R5 virus), while T-tropic HIV-1 preferentially uses CXCR4 (X4 virus). Dual tropic HIV-1 is capable of using either CXCR4 or CCR5.3 However, since both macrophages and T cells are capable of expressing CCR5 and CXCR4, and each cell type is capable of supporting infection by either strain of virus, coreceptor use and tropism can be discordant. Often, there is a transition during infection from R5 to X4 tropism. R5 virus initially infects mucosal dendritic cells and macrophages, and memory CD4 T cells that express CCR5, especially in the gut-associated lymphoid tissue (GALT), are subsequently infected. Macrophages and T cells harboring R5 HIV disseminate and establish reservoirs in various compartments (see Gorry and Ancuta3 for a review of viral reservoirs). X4 tropic HIV typically arises later in infection and is associated with a rapid decline in CD4 T cells, CD8 cell apoptosis, and an impaired humoral response, suggesting a link between the emergence of X4 tropic virus, clinical deterioration, and progression to AIDS. However, since HIV continues to mutate during the entire course of infection, individual infections can end up advancing to any permutation of X4, R5, or dual tropic virus.
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