Computational Modelling of Intracellular Viral Kinetics and CD4+ Cellular Population Dynamics of HIV/AIDS.
Computational microepidemiologic modelling can facilitate the understanding of complex biomedical systems. It provides novel methods for quantitatively studying population health dynamics from the micro level of genomes and molecules to the higher macro levels such as HIV/AIDS in humans. Untangling the dynamics between the human immunodeficiency virus-1 (HIV-1) and CD4(+) lymphocyte populations and intracellular molecular kinetics of interactions in an integrative systems dynamics approach can help to understand the effective points of interventions in the HIV life cycle. With that in mind, we have developed a stochastic systems dynamics model that includes intracellular molecular level interactions. A sequence of events, molecular interactions and cytochemical kinetics are triggered when the HIV infects a CD4(+) lymphocyte. The full sequence of molecular level dynamics includes: attachment and fusion; reverse transcription; integration; transcription; translation; and budding or release of new virus. The newly released virus circulates back and infects a new CD4(+) lymphocyte and the cycle continues repeatedly. Mathematical models that account for these processes were developed. The model developed provides insights into how an intracellular/molecular level model can be incorporated within a macro-epidemiologic integrative systems dynamics model for examining a variety of computational experimentations. Such experimentations can help in evaluating scientific questions related to effective strategies in HIV drug therapy interventions.
Tameru
Berhanu
B
Center for Computational Epidemiology, Bioinformatics & Risk Analysis (CCEBRA), College of Veterinary Medicine, Nursing & Allied Health, Tuskegee University, Tuskegee, AL 36088, http://compepid.tuskegee.edu.
Habtemariam
Tsegaye
T
Nganwa
David
D
Ayanwale
Lekan
L
Beyene
Gemechu
G
Robnett
Vinaida
V
Wilson
Wanda
W
Nature. 1995 Jan 12;373(6510):123-6
7816094
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3862-6
8171003
Nature. 1995 Jan 12;373(6510):117-22
7529365
Virology. 1992 Apr;187(2):398-406
1347667
Science. 1995 Jan 27;267(5197):483-9
7824947
EMBO J. 2001 Apr 2;20(7):1726-38
11285236
Cell Mol Biol (Noisy-le-grand). 2001 Nov;47(7):1201-8
11838968
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13925-30
11717449
Science. 1996 Mar 15;271(5255):1582-6
8599114
AIDS Res Hum Retroviruses. 1999 Feb 10;15(3):273-83
10052758
J Virol. 2001 Jan;75(2):759-71
11134289
J Virol. 1997 Jul;71(7):5382-90
9188609
AIDS Res Hum Retroviruses. 1993 Sep;9(9):817-23
7504934