to establish infection. Thus, the binding specificity of viral surface proteins dictates tropism as well as the destruction of particular cell populations, and is therefore a major determinant of virus pathogenesis. However, co-receptors are sometimes required in addition to the binding of cellular receptors on host cells to viral proteins in order to establish infection. For instance, HIV-1 requires target cells to express co-receptors CCR5 or CXCR4, on top of the CD4 receptor for productive viral attachment. Interestingly, HIV-1 can undergo a tropism switch, where the virus glycoprotein gp120 initially uses CCR5 (mainly on macrophages) as the primary co-receptor for entering the host cell. Subsequently, HIV-1 switches to bind to CXCR4 (mainly on T cells) as the infection progresses, in doing so transitions the viral pathogenicity to a different stage. Apart from cellular receptors, viral tropism can also governed by other intracellular factors, such as tissue-specific transcription factors. An example would be the JC polyomavirus, in which its tropism is limited to glial cells since its enhancer is only active in glial cells, and JC viral gene expression requires host transcription factors expressed exclusively in glial cells. The accessibility of host tissues and organs to the virus also regulates tropism. Accessibility is affected by physical barriers, such as in enteroviruses, which replicate in the intestine since they are able to withstand bile, digestive enzymes and acidic environments. Virus factors Viral genetics encoding viral factors will determine the degree of viral pathogenesis. This can be measured as virulence, which can be used to compare the quantitative degree of pathology between related viruses. In other words, different virus strains possessing different virus factors can lead to different degrees of virulence, which in turn can be exploited to study the differences in pathogenesis of viral variants with different virulence. Virus factors are largely influenced by viral genetics, which is the virulence determinant of structural or non-structural proteins and non-coding sequences. For a virus to successfully infect and cause disease in the host, it has to encode specific virus factors in its genome to overcome the preventive effects of physical barriers, and modulate host inhibition of virus replication. In the case of poliovirus, all vaccine strains found in the oral polio vaccine contain attenuating point mutations in the 5' untranslated region (5' UTR). Conversely, the virulent strain responsible for causing polio disease does not contain these 5' UTR point mutations and thus display greater