Cell-to-cell transmission promotes the emergence of double-drug resistance

Saeki, K. & Sasaki, A. ORCID: https://orcid.org/0000-0003-3582-5865 (2023). Cell-to-cell transmission promotes the emergence of double-drug resistance. Virus Evolution 9 (1) vead017. 10.1093/ve/vead017.

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The use of multiple antivirals in a single patient increases the risk of emergence of multidrug-resistant viruses, posing a public health challenge and limiting management options. Cell-to-cell viral transmission allows a pair of viruses that are each resistant to a single drug to persist for a prolonged period of passages although neither can survive alone under double-drug treatment. This pair should then persist until they accumulate a second mutation to generate resistance to both drugs. Accordingly, we here propose a hypothesis that viruses have a much higher probability of developing double-drug resistance when they are transmitted via a cell-to-cell mode than when they are transmitted via a cell-free mode through released virions. By using a stochastic model describing the changes in the frequencies of viral genotypes over successive infections, we analytically demonstrate that the emergence probability of double resistance is approximately the square of the number of viral genomes that establish infection times greater in cell-to-cell transmission than in cell-free transmission. Our study suggests the importance of inhibiting cell-to-cell transmission during multidrug treatment.

Item Type: Article
Uncontrolled Keywords: cell dynamics; cell-to-cell transmission; intra-host viral dynamics; multiple-drug-resistance; Wright-Fisher model with killing
Research Programs: Evolution and Ecology (EEP)
Depositing User: Luke Kirwan
Date Deposited: 25 May 2023 10:10
Last Modified: 25 Sep 2023 12:52
URI: https://pure.iiasa.ac.at/18819

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