Late-emerging strains of HIV induce T-cell homeostasis failure by promoting bystander cell death and immune exhaustion in naïve CD4 and all CD8 T-cells.
The mechanisms involved in the decline of CD4 and CD8 T-cells that lead to HIV-induced immune dysregulation are not clearly understood. We hypothesize that late-emerging strains of HIV, such as CXCR4-tropic (X4) virions, induce T-cell homeostasis failure by promoting significantly more bystander cell death, and immune exhaustion in naïve CD4 and all CD8 T-cells, when compared to strain of HIV, such as CCR5-tropic (R5) virions, found early during the course of infection. In the reported study, inactivated X4 virions induced greater bystander cell death in sort-purified naïve CD4 T-cells compared to R5 virions, which was significant (p=0.013), and in memory CD8 T-cells, though the latter was not significant. A clearer understanding of the mechanisms involved in HIV-induced depletion of T-cell numbers and function could lead to therapies that prevent T-cell death and restore immune function. These therapies could improve current anti-retroviral and cure-related treatments by boosting the immune system's own ability to combat the virus.
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States. Electronic address: ckibiri1@jhu.edu.
Catherine N
CN
Kibirige
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.
Frederick A
FA
Menendez
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.
Hao
H
Zhang
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.
Tricia L
TL
Nilles
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.
Susan
S
Langan
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.
Joseph B
JB
Margolick
D024201:Bystander Effect; D016923:Cell Death; D006678:HIV / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*