Nature Medicine
5, 211 - 216 (1999)
doi:10.1038/5576
Human immunodeficiency virus type 1 neutralizing antibodies accelerate
clearance of cell−free virions from blood plasmaTatsuhiko Igarashi1, Charles Brown1, Ali Azadegan2, Nancy Haigwood3, Dimiter Dimitrov4, Malcolm A. Martin1
& Riri Shibata1, 51
Laboratory of Molecular Microbiology, National Institute
of Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, Maryland 20892, USA
2
Veterinary Resource Program, National Institutes of
Health, Bethesda, Maryland 20892,
USA
3
Seattle Biomedical Research Institute, Seattle, Washington 98109, USA
4
Laboratory of Experimental and Computational Biology, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA
5
R.S. present address: VaxGen, 1000 Marina Boulevard, Brisbane, California 94005−1841, USA
The concentration of human immunodeficiency virus type 1 (HIV−1)
particles in blood plasma is very predictive of the subsequent disease course
in an infected individual; its measurement has become one of the most important
parameters for monitoring clinical status1. Steady−state
virus levels in plasma reflect a balance between the rates of virions entering
and leaving the peripheral blood2. We analyzed the rate of virus
clearance in the general circulation in rhesus macaques receiving a continuous
infusion of cell−free particles in the presence and absence of virus−specific
antibodies. Here we show, by measuring virion RNA, particle−associated
p24 Gag protein and virus infectivity, that the clearance of physical and
infectious particles from a primary, dual−tropic virus isolate, HIV−1
DH12, is very rapid in naive animals, with half−lives ranging
from 13 to 26 minutes. In the presence of high−titer HIV−1
DH12−specific neutralizing antibodies, the half−life of
virion RNA was considerably reduced (to 3.9−7.2 minutes), and infectious
virus in the blood became undetectable. Although physical virus particles
were eliminated extravascularly, the loss of virus infectivity in the blood
reflected the combined effects of extravascular clearance and intravascular
inactivation of HIV−1 infectivity due to antibody binding.
|
