The cell tropism of human immunodeficiency virus type 1 determines the kinetics of plasma viremia in SCID mice reconstituted with human peripheral blood leukocytes.
Most individuals infected with human immunodeficiency virus type 1 (HIV-1) initially harbor macrophage-tropic, non-syncytium-inducing (M-tropic, NSI) viruses that may evolve into T-cell-tropic, syncytium-inducing viruses (T-tropic, SI) after several years. The reasons for the more efficient transmission of M-tropic, NSI viruses and the slow evolution ofT-tropic, SI viruses remain unclear, although they may be linked to expression of appropriate chemokine coreceptors for virus entry. We have examined plasma viral RNA levels and the extent of CD4+ T-cell depletion in SCID mice reconstituted with human peripheral blood leukocytes following infection with M-tropic, dual-tropic, or T-tropic HIV-1 isolates. The cell tropism was found to determine the course of viremia, with M-tropic viruses producing sustained high viral RNA levels and sparing some CD4+ T cells, dual-tropic viruses producing a transient and lower viral RNA spike and extremely rapid depletion of CD4+ T cells, and T-tropic viruses causing similarly lower viral RNA levels and rapid-intermediate rates of CD4+ T-cell depletion. A single amino acid change in the V3 region of gp120 was sufficient to cause one isolate to switch from M-tropic to dual-tropic and acquire the ability to rapidly deplete all CD4+ T cells.
Picchio
G R
GR
Department of Immunology-IMM7, The Scripps Research Institute, La Jolla, California 92037, USA.
Gulizia
R J
RJ
Wehrly
K
K
Chesebro
B
B
Mosier
D E
DE
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004195:Disease Models, Animal; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D012367:RNA, Viral / Q000096:biosynthesis; D014766:Viremia; D014779:Virus Replication
D012367:RNA, Viral