Contribution of HIV-1 genomes that do not integrate to the basic reproductive ratio of the virus

JOURNAL OF THEORETICAL BIOLOGY

卷:367

Article

Lau, John Wei¹  Levy, David N.²  Wodarz, Dominik¹ 

[1] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA

[2] NYU, Coll Dent, Dept Basic Sci, New York, NY 10010 USA

关键词: Virus dynamics;    HIV dynamics;    Unintegrated HIV;   

DOI  :  10.1016/j.jtbi.2014.12.004

来源: Elsevier

【 摘 要 】

Recent experimental data indicate that HIV-1 DNA that fails to integrate (from now on called uDNA) can by itself successfully produce infectious offspring virions in resting T cells that become activated after infection. This scenario is likely important at the initial stages of the infection. We use mathematical models to calculate the relative contribution of unintegrated and integrated viral DNA to the basic reproductive ratio of the virus, R-0, and the models are parameterized with preliminary data. This is done in the context of both free virus spread and transmission of the virus through virological synapses. For free virus transmission, we find that under preliminary parameter estimates, uDNA might contribute about 20% to the total R-0. This requires that a single copy of uDNA can successfully replicate. If the presence of more than one uDNA copy is required for replication, uDNA does not contribute to R-0. For synaptic transmission, uDNA can contribute to R-0 regardless of the number of uDNA copies required for replication. The larger the number of viruses that are successfully transmitted per synapse, however, the lower the contribution of uDNA to R-0 because this increases the chances that at least one virus integrates. Using available parameter values, uDNA can maximally contribute 20% to R-0 in this case. We argue that the contribution of uDNA to virus reproduction might also be important for continued low level replication of HIV-1 in the presence of integrase inhibitor therapy. Assuming a 20% contribution of uDNA to the overall R-0, our calculations suggest that R-0 = 1.6 in the absence of virus integration. While these are rough estimates based on preliminary data that are currently available, this analysis provides a framework for future experimental work which should directly measure key parameters. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

Free