Theiler's virus persists in the white matter of the spinal cord of genetically susceptible mice and causes primary demyelination. The virus persists in macrophages/microglial cells, but also in oligodendrocytes, the myelin-forming cells. Susceptibility/resistance to this chronic infection has been mapped to several loci including one tentatively located in the telomeric region of chromosome 18,...

The geminivirus replication protein AL1 interacts with retinoblastoma-related protein (RBR), a key regulator of the plant division cell cycle, to induce conditions permissive for viral DNA replication. Previous studies of tomato golden mosaic virus (TGMV) AL1 showed that amino acid L148 in the conserved helix 4 motif is critical for RBR binding. In this work, we examined the effect of an L148V ...

Viral particles (virions) are made of genomic material packaged with proteins, drawn from the pool of proteins in the parent cell. It is well known that when virion concentrations are high, cells can be coinfected with multiple viral strains that can complement each other. Viral genomes can then interact with proteins derived from different strains, in a phenomenon known as phenotypic mixing. B...

The rapid evolution of Human Immunodeficiency Virus (HIV-1) allows studies of ongoing host-pathogen interactions. One key selective host factor is APOBEC3G (hA3G) that can cause extensive and inactivating Guanosine-to-Adenosine (G-to-A) mutation on HIV plus-strand DNA (termed hypermutation). HIV can inhibit this innate anti-viral defense through binding of the viral protein Vif to hA3G, but bin...

In this paper, we present a general selection-mutation model of evolution on a one-dimensional continuous fitness space. The formulation of our model includes both the classical diffusion approach to mutation process as well as an alternative approach based on an integral operator with a mutation kernel. We show that both approaches produce fundamentally equivalent results. To illustrate the su...

Mutation is the basis of adaptation. Yet, most mutations are detrimental, and elevating mutation rates will impair a population's fitness in the short term. The latter realization has led to the concept of lethal mutagenesis for curing viral infections, and work with drugs such as ribavirin has supported this perspective. As yet, there is no formal theory of lethal mutagenesis, although referen...

We previously identified a rare mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), I132M, which confers high-level resistance to the nonnucleoside RT inhibitors (NNRTIs) nevirapine and delavirdine. In this study, we have further characterized the role of this mutation in viral replication capacity and in resistance to other RT inhibitors. Surprisingly, our data ...

Viral mutation rates vary widely in nature, yet the mechanistic and evolutionary determinants of this variability remain unclear. Small DNA viruses mutate orders of magnitude faster than their hosts despite using host-encoded polymerases for replication, which suggests these viruses may avoid post-replicative repair. Supporting this, the genome of bacteriophage ϕX174 is completely devoid of GAT...

Cytomegalovirus encephalitis occurs rarely in transplant recipients. We describe a patient with cytomegalovirus ventriculoencephalitis who had a very high CSF viral load but a low peripheral blood viral load. No resistance mutations were present in cerebrospinal fluid viral DNA, whereas DNA from blood showed a resistance mutation in the UL54 gene but not in the UL97 gene. Viral replication was ...