Viral pathogenesis
Viral pathogenesis is the study of the process and mechanisms by which viruses cause diseases in their target hosts, often at the cellular or molecular level.
In order to cause disease, the virus must also overcome several inhibitory effects present in the host.
Here, the virus must modulate the host innate immune response to prevent its elimination by the body while facilitating its replication.
[2][7] Notably, the poliovirus can be transmitted via the fecal-oral route, where it initially replicates in its site of entry, the small intestine and spread to regional lymph nodes.
The respiratory, alimentary and urogenital tracts and the blood are the most frequent sites of shedding in the form of bodily fluids, aerosols, skin, excrement.
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.
[2][7] 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.
[8] 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.
Accessibility is affected by physical barriers,[2][7] such as in enteroviruses, which replicate in the intestine since they are able to withstand bile, digestive enzymes and acidic environments.
[10][11] Virus factors are largely influenced by viral genetics, which is the virulence determinant of structural or non-structural proteins and non-coding sequences.
Conversely, the virulent strain responsible for causing polio disease does not contain these 5' UTR point mutations and thus display greater viral pathogenicity in hosts.
[13][14] As such, viruses capable of manipulating the host cell response to infection as an immune evasion strategy exhibit greater pathogenicity.
In particular, genetic factors, age and immunocompetence play an important role is dictating whether the viral infection can be modulated by the host.
[11][15] Mice that possess functional Mx genes encode an Mx1 protein which can selectively inhibit influenza replication.
[16] Alternatively, immunocompromised individuals due to existing illnesses may have a defective immune system which makes them more vulnerable to damage by the virus.
[15][22][18] Viruses such as the human papillomavirus (HPV), human T-lymphotropic virus (HTLV) etc., can stimulate growth of tumours in infected hosts, either by disrupting tumour suppressor gene expression (HPV) or upregulating proto-oncogene expression (HTLV).
[15] Sometimes, instead of cell death or cellular dysfunction caused by the virus, the host immune response can mediate disease and excessive inflammation.
[23][24] Specifically, immunopathology is caused by the excessive release of antibodies, interferons and pro-inflammatory cytokines, activation of the complement system, or hyperactivity of cytotoxic T cells.
[26] The bystander mechanism hypothesizes the initiation of a non-specific and overreactive antiviral response that tackles self-antigens in the process.
[7][28] Surprisingly, generalised infections by togaviruses have a short incubation period due to the direct entry of the virus into target cells through insect bites.
A successful pathogen needs to spread to at least one other host, and lower virulence can result in higher transmission rates under some circumstances.
