Question

What are some ways quasispecies can contribute to pathogenesis of a virus such as HIV?

Answer 1

The generation of HIV quasispecies in infected host is driven principally by the low replicative fidelity of HIV reverse transcriptase , the rapid kinetics of HIV replication, aspects of the HIV replicative cycle itself that are conducive to mutagenesis, and viral genetic recombination.

The multiple environments in which viruses have to replicate in vivo may promote the selective expansion of subpopulations from viral quasispecies thereby leading to variant viruses that display altered relative fitness in the different host organs, as compared with their parental populations. The narrative on the error -prone replication of viruses is amplified by bringing principles to bear on the generation of variant genomes as a result , viral quasispecies and how these viral populations behave. Chronic HIV infection is characterized by marked genotypic heterogeneity of the systemic virus pool.

Increased rates of Vittal replication associated with immune-activating stimuli may promote further genotypic diversification by mutation or by leading to additional expression of previously latent proviral genotypes. It is hypothesized, that by these means new viral quasispecies able to evade the eatablished host anti-viral responses, increasing viral replication and disease progression, may be expressed.

Some analysis demonstrate that for some NRTIs and ritonavir-boosted protease inhibitors there is a broad range of resistance patterns against which the drugs retain partial antiviral efficacy. In contrast for 3TC, FTC, NNRTIs and enfuvirtide, resistance tend to be more of an all-or-nothing phenomenon. Incorporation of these clinical cut off values provides an attractive rational tool to objectively select the next optimal antiretroviral treatment regimen for treatment experienced HIV positive subjects.