Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor: role of the envelope.
Loss of T cell homeostasis usually precedes the onset of AIDS. We hypothesized that rapid progressors may be transmitted with HIV-1 that is particularly able to perturb T cell homeostasis. To this end, we have tested two transmitted, syncytium-inducing (SI) viral isolates from a rapid progressor in two thymus models. One of the isolates (R3A) exhibited markedly rapid kinetics of replication and thymocyte depletion. These phenotypes mapped to the envelope, as a recombinant NL4-3 virus encoding the R3A envelope had similar phenotypes, even in the absence of nef. Notably, the viruses with high pathogenic activity in the thymus (R3A and NL4-R3A) did not show enhanced replication or cytopathicity in PHA-stimulated PBMCs. Furthermore, NL4-R3A did not enhance replication of the coinfected NL4-3 virus in the thymus, suggesting an intrinsic advantage of the R3A envelope. The R3A envelope showed higher entry activity in infecting human T cells and in depleting CD4+ thymocytes when expressed in trans. These data suggest that SI viruses with unique envelope functions which can overcome barriers to transmission may hasten disease progression by perturbing T cell homeostasis.
Meissner
Eric G
EG
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Duus
Karen M
KM
Gao
Feng
F
Yu
Xiao-Fang
XF
Su
Lishan
L
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D002452:Cell Count; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D017353:Gene Deletion; D015693:Gene Products, nef / Q000172:deficiency / Q000235:genetics; D015658:HIV Infections / Q000175:diagnosis / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010641:Phenotype; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015693:Gene Products, nef; D014759:Viral Envelope Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus