Both Memory and CD45RA+/CD62L+ Naive CD4+ T Cells Are Infected in Human Immunodeficiency Virus Type 1-Infected Individuals

AUTOR(ES)

Ostrowski, Mario A.

FONTE

American Society for Microbiology

RESUMO

Cellular activation is critical for the propagation of human immunodeficiency virus type 1 (HIV-1) infection. It has been suggested that truly naive CD4+ T cells are resistant to productive HIV-1 infection because of their constitutive resting state. Memory and naive CD4+ T-cell subsets from 11 HIV-1-infected individuals were isolated ex vivo by a combination of magnetic bead depletion and fluorescence-activated cell sorting techniques with stringent criteria of combined expression of CD45RA and CD62L to identify naive CD4+ T-cell subsets. In all patients HIV-1 provirus could be detected within naive CD45RA+/CD62L+ CD4+ T cells; in addition, replication-competent HIV-1 was isolated from these cells upon CD4+ T-cell stimulation in tissue cultures. Memory CD4+ T cells had a median of fourfold more replication-competent virus and a median of sixfold more provirus than naive CD4+ T cells. Overall, there was a median of 16-fold more integrated provirus identified in memory CD4+ T cells than in naive CD4+ T cells within a given patient. Interestingly, there was a trend toward equalization of viral loads in memory and naive CD4+ T-cell subsets in those patients who harbored CXCR4-using (syncytium-inducing) viruses. Within any given patient, there was no selective usage of a particular coreceptor by virus isolated from memory versus naive CD4+ T cells. Our findings suggest that naive CD4+ T cells may be a significant viral reservoir for HIV, particularly in those patients harboring CXCR4-using viruses.

Documentos Relacionados

• Contact of human immunodeficiency virus type 1-infected and uninfected CD4+ T lymphocytes is highly cytolytic for both cells.
• Decreased effector memory CD45RA+ CD62L- CD8+ T cells and increased central memory CD45RA- CD62L+ CD8+ T cells in peripheral blood of rheumatoid arthritis patients
• Loss of CD4+ T Cells in Human Immunodeficiency Virus Type 1-Infected Chimpanzees Is Associated with Increased Lymphocyte Apoptosis
• Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals.
• Memory Responses in Human Immunodeficiency Virus Type 1-Infected Individuals with Long-Term Viral Load Suppression Are Independent of CD4 Cell Nadir