What do mathematical models tell us about killing rates during HIV-1 infection?
Over the past few decades the extent to which cytotoxic T lymphocytes (CTLs) control human immunodeficiency virus (HIV) replication has been studied extensively, yet their role and mode of action remain controversial. In some studies, CTLs were found to kill a large fraction of the productively infected cells relative to the viral cytopathicity, whereas in others CTLs were suggested to kill only a small fraction of infected cells. In this review, we compile published estimates of CTL-mediated death rates, and examine whether these studies permit determining the rate at which CTLs kill HIV-1 infected cells. We highlight potential misinterpretations of the CTL-killing rates from the escape rates of mutants, and from perturbations of the steady state viral load during chronic infection. Our major conclusion is that CTL-mediated killing rates remain unknown. But contrary to current consensus, we argue that killing rates higher than one per day are perfectly consistent with the experimental data, which would imply that the majority of the productively infected cells could still die from CTL-mediated killing rather than from viral cytopathicity.
Theoretical Biology and Bioinformatics, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. Electronic address: s.gadhamsetty@uu.nl.
Saikrishna
S
Gadhamsetty
Division of Toxicology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Joost B
JB
Beltman
Theoretical Biology and Bioinformatics, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Rob J
RJ
de Boer
D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D057131:Immune Evasion / Q000235:genetics / Q000276:immunology; D018448:Models, Immunological; D008962:Models, Theoretical; D009154:Mutation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology