Viral mutation

A final but important consideration is viral mutation. Certain mutant HIV strains are resistant to one or more of the protease inhibitors, and even for patients who respond initially to protease inhibitors it is possible that mutant viral forms may eventually thrive in the infected individual. The search for new and more effective protease inhibitors is ongoing. 

Variant nucleotides, 34 Variants catalog, 40 Venter, Craig, 114 Vertical expansion, 126 Vibrio cholera, 148 Vickers, Philip, 129 Viral mutations, 96 Voluntary health agencies, 4... 

Moreover, the discovery of effective agents to treat infectious diseases such as malaria and tuberculosis is inherently difficult - bacterial resistance and viral mutations are common, so that therapies have very limited efficacy, and a discovery platform in infectious disease is a multi-year commitment of financial and other research resources. Again, developmental failures are expensive and R D expenditures are what economists call "sunk costs," meaning that the costs are not recoverable in the future. 

Efavirenz (DMP 266) (1) is an effective non-nucleoside inhibitor of reverse transcriptase of the human immunodeficiency virus (HIV) recently registered by the US Food Drug Administration (FDA) for treatment of the acquired immunodeficiency syndrome (AIDS).1 2 3 Inhibition of HIV reverse transcriptase by nucleosides like azidothymidine (AZT) (2) is a proven therapy for delaying the progression to AIDS. However, the rapid viral mutation to resistant strains requires the development of new therapeutic agents. The recent development of both protease inhibitors and non-nucleoside reverse transcriptase inhibitors offers hope of effective treatment especially when coadministered. 

Lentivirus + + + Life-long +++ Quiescent and dividing Cytotoxicity Viral mutation +... 

The quasispecies model defines an optimal mutation rate for evolving populations (Eigen et al., 1988). At the critical mutation rate pmml (referred to as the error threshold), the distribution becomes too broad for selection to withstand the dispersion and it wanders stochastically on the fitness landscape. The optimal mutation rate for evolvability should be as close to pm Crit as possible without exceeding it. Indeed, it was found that viral mutation rates are very close to pm m,. By assuming that the mutation probability is the same at each residue, the error threshold in terms of mutation rate pm ai, was derived as... 

Fig. 3. The strategy for detecting viral mutations is represented. Differences between two strains of a virus are characterized by comparing mass spectra of proteolytic fragments. The specific peptide ion modification can then be localized by tandem mass spectrometry in combination with MALDI or ESI...

Viral mutation. An mRNA transcript of a T7 phage gene contains the base sequence... 

Resistance can occur through a number of consequences of viral mutation. There may be reduced phosphorylation of the dmg (for example with nucleoside analogues), alteration of viral enzyme targets (for example with reverse transcriptase inhibitors), or alteration of target channel protein (for example with amantadine). 

Viral mutation via the animal reservoir could result in a highly infectious form of the virus amongst humans, and could instigate a global pandemic. 

Table 1 lists the selenoproteins that have been unequivocally identified in mammals, together with a summary of their main locations and known functions. Of the known glutathione peroxidases, three are tetramers and one (the phospholipid hydroperoxide-specific peroxidase) is monomeric in its quaternary structure. It appears to be this class of enzymatic activity that is critical for the action of selenoproteins in maintaining immune function, and indeed, glutathione peroxidase type I knockout mice are susceptible to viral mutation and increased viral virulence, as are selenium-deficient ones. Several other selenoproteins listed in Table 1 also have antioxidant functions and... 

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