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 Molecular basis of virus tropism Virus tropism refers to the virus' preferential site of replication in discrete cell types within an organ. In most cases, tropism is determined by the ability of the viral surface proteins to fuse or bind to surface receptors of specific target cells