Quantitation of human immunodeficiency virus type 1 infection kinetics.
Tissue culture infections of CD4-positive human T cells by human immunodeficiency virus type 1 (HIV-1) proceed in three stages: (i) a period following the initiation of an infection during which no detectable virus is produced; (ii) a phase in which a sharp increase followed by a peak of released progeny virions can be measured; and (iii) a final period when virus production declines. In this study, we have derived equations describing the kinetics of HIV-1 accumulation in cell culture supernatants during multiple rounds of infection. Our analyses indicated that the critical parameter affecting the kinetics of HIV-1 infection is the infection rate constant k = Inn/ti, where n is the number of infectious virions produced by one cell (about 10(2)) and ti is the time required for one complete cycle of virus infection (typically 3 to 4 days). Of particular note was our finding that the infectivity of HIV-1 during cell-to-cell transmission is 10(2) to 10(3) times greater than the infectivity of cell-free virus stocks, the inocula commonly used to initiate tissue culture infections. We also demonstrated that the slow infection kinetics of an HIV-1 tat mutant is not due to a longer replication time but reflects the small number of infectious particles produced per cycle.
Dimitrov
D S
DS
Section on Membrane Structure and Function, National Cancer Institute, Bethesda, Maryland 20892.
Willey
R L
RL
Sato
H
H
Chang
L J
LJ
Blumenthal
R
R
Martin
M A
MA
D002449:Cell Aggregation; D003588:Cytopathogenic Effect, Viral; D015658:HIV Infections / Q000382:microbiology*; D015497:HIV-1 / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D013997:Time Factors; D014779:Virus Replication