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. It is a specialized field of study in virology. Pathogenesis is a qualitative description of the process by which an initial infection causes disease. Viral disease is the sum of the effects of viral replication on the host and the host's subsequent immune response against the virus. Viruses are able to initiate infection, disperse throughout the body, and replicate due to specific virulence factors. There are several factors that affect pathogenesis. Some of these factors include virulence characteristics of the virus that is infecting. In order to cause disease, the virus must also overcome several inhibitory effects present in the host. Some of the inhibitory effects include distance, physical barriers and host defenses. These inhibitory effects may differ among individuals due to the inhibitory effects being genetically controlled. Viral pathogenesis is affected by various factors: (1) transmission, entry and spread within the host, (2) tropism, (3) virus virulence and disease mechanisms, (4) host factors and host defense.
Mechanisms of infection Viruses need to establish infections in host cells in order to multiply. For infections to occur, the virus has to hijack host factors and evade the host immune response for efficient replication. Viral replication frequently requires complex interactions between the virus and host factors that may result in deleterious effects in the host, which confers the virus its pathogenicity.
Important steps of a virus life cycle that shape pathogenesis
Transmission from a host with an infection to a second host Entry of the virus into the body Local replication in susceptible cells Dissemination and spread to secondary tissues and target organs Secondary replication in susceptible cells Shedding of the virus into the environment Onward transmission to third host
Primary transmission Three requirements must be satisfied to ensure successful infection of a host. Firstly, there must be sufficient quantity of virus available to initiate infection. Cells at the site of infection must be accessible, in that their cell membranes display host-encoded receptors that the virus can exploit for entry into the cell, and the host anti-viral defense systems must be ineffective or absent.
Entry to host Viruses causing disease in humans often enter through the mouth, nose, genital tract, or through damaged areas of skin, so cells of the respiratory, gastrointestinal, skin and genital tissues are often the primary site of infection. Some viruses are capable of transmission to a mammalian fetus through infected germ cells at the time of fertilization, later in pregnancy via the placenta, and by infection at birth.
Local replication and spread Following initial entry to the host, the virus hijacks the host cell machinery to undergo viral amplification. Here, the virus must modulate the host innate immune response to prevent its elimination by the body while facilitating its replication. Replicated virus from the initially infected cell then disperse to infect neighbouring susceptible cells, possibly with spread to different cell types like leukocytes. This results in a localised infection, in which the virus mainly spreads and infects adjacent cells to the site of entry. Otherwise, the virus can be released into extracellular fluids. Examples of localised infections include: common cold (rhinovirus), flu (parainfluenza), gastrointestinal infections (rotavirus) or skin infections (papillomavirus).
Dissemination and secondary replication In other cases, the virus can cause systemic disease through a disseminated infection spread throughout the body. The predominant mode of viral dissemination occurs through the blood or lymphatic system, some of which include viruses responsible for chickenpox (varicella zoster virus), smallpox (variola), HIV (human immunodeficiency virus). A minority of viruses can disseminate via the nervous system. 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. Then, the virus disseminates via the bloodstream into different organs in the body (e.g. liver, spleen), followed by a secondary round of replication and dissemination into the central nervous system to damage motor neurons.
Shedding and secondary transmission Finally, the viruses spread to sites where shedding into the environment can occur. 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. The virus would then go on to be transmitted to another person, and establish the infection cycle all over again.
Factors affecting pathogenesis There are a few main overarching factors affecting viral diseases:
Virus tropism Virus factors Host factors
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