HIV-1-associated pathology in hemato-lymphoid organs and the experimental evaluation in the SCID-hu mouse.
A variety of possible mechanisms for the loss of CD4+ T cells has been proposed, such as direct cytopathic effects by HIV-1 infection, and indirect induction of apoptosis. However, the fundamental picture of major and central pathogenic processes for the decay of immune systems is still missing in understanding the pathogenic mechanisms of HIV-1 infected humans. It is more appropriate to expand our focus onto entire organ systems involved in the development of immune system such as bone marrow and thymus. From the observations in the clinical studies, HIV-1 causes a variety of pathology on the T cell development pathway even from the hematopoietic progenitors and immature thymocytes, which should have a substantial impact on the failure of T cell homeostasis in the periphery. The SCID-hu mouse constructed by surgical implantation of human fetal hemato-lymphoid organs into the immunodeficient mouse has been used for the experimental evaluation of various parameters associated with HIV-1 infection and hematosuppression. Given the apparently normal structure and function of the human implants, the SCID-hu bone and Thy/Liv mice would appear to be potentially reliable models for the analysis of human physiology and patho-physiology.
Kaneshima
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HIV Gene Therapy/Pathogenesis Research SyStemix, Inc., Palo Alto, CA 94304, USA. hkaneshima@stem.com
D017088:AIDS-Related Opportunistic Infections / Q000473:pathology; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis; D001853:Bone Marrow / Q000196:embryology / Q000473:pathology; D016026:Bone Marrow Transplantation; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D004353:Drug Evaluation, Preclinical; D016332:Fetal Tissue Transplantation; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008099:Liver / Q000196:embryology; D016031:Liver Transplantation; D008221:Lymphoid Tissue / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D013950:Thymus Gland / Q000196:embryology / Q000473:pathology / Q000637:transplantation*; D014183:Transplantation, Heterologous
D000998:Antiviral Agents; D016207:Cytokines