See also anti-viral agents  

Introduction:

To establish an infection and casue disease, a virus must first have access to tissues in the body. Although skin is exposed, the most common point of infection is respiratory epithelia because skin has multiple layers, the outermost of which is keratinized and slightly acidic. In adition to lack the protective features of skin, respiratory epithelia have a surface rea about 70 times that of skin which is continuously epxosed to potentially virus containing air one breaths. However, viruses can breach the skin barrier where it is broken by injury, insects or medical procedures. Viruses can also gain entry to the body at the gastrointestinal mucosa, the surface of the eye and the urogenital epithelia.

Once a virus has infected a cell at the site of entry, it must relicate in that cell. Viruses can spread in blood, lymph or via neurological tissue. In blood and lymph, viruses may be assocaited with immunoglogical cells or be freely circulating (viremia). Acute infection involves parid replication of virus whcih can lead to a sudden onset of symptoms..

Many factors affect whether you will be more or less susceptible to viral infection and the course of a viral infection. Factors which are important include the genotype of the virus, your own ethnic background, your gender and your age. Lets take genetic background as an example since it clearly is a major factor.

Activation of Oncogenes leading to Cancer: 

About 15% of all malignant cancers are also caused by viruses. Hepatitus B virus, for example, is associated with liver carcinoma. Certain types of papillomarviruses are associated with cervical and penile cancer. These types of exist as an episomal viral DNA and integrate into the host DNA thereby disrupting the negative regulator E2 resulting in strong activation of E6 and E7 oncogenes that bind and inactivate p53 and Rb.

Importance of Genetic Host Background: 

Just as the genotype of the invading virus can influence the course of a viral infection, so too can the genetic background of the invaded host. For example, mousepox is a generalized infection caused by the ectroemlia virus, which is an inapparent disease in the genetically resistant C57B1/6 mouse strain. On the other hand, only one infectious particle of the same virus can result in 100% mortality in the sensitive BALB/c or A mouse strains.

This difference in strain susceptibility is related to differences in the cytokine profile produced after infection. In the C57B1/6 strain, there is a rapid induction of type 1 cytokines and a potent cytotoxic T lymphocyte response, whereas in the BALB/c or A mice these cytokines are virtually absent with a complete absence or delayed induction of a CTL response.

The importance of genetic background in viral infection has been shown in mice. To take an example, mousepox is a generalized infection caused by the ectromelia virus. This virus does nothing to the genetically resitant C57B1/6 mouse strain. In contrast, only one infectious particle of the same virus can result in 100% mortality in the sensitive BALB/c or A mouse strains. Why is this so? The reason for the difference in strain susceptibility is related to differences in the cytokine profile produced in each of these strains after infection. In the C57B1/6 strain, there is a rapid induction of type 1 cytokines (interleukin-2, interferon-y, tumor necrosis factor-alpha) which results in a potent cytotoxic T lymphocyte (CTL) immune response. However in the BALB/c or A mice these cytokines are virtually absent with a complete absence or delayed induction of a CTL response.

Importance of Genotype of the Virus: 

This is just one example where certain viruses are lethal in one type of mouse strain but do absolutely nothing in other strains. Clearly the differences seem to lie in the genetic makeup of these different strains. A different genetic makeup can result in a different immune response which either confers resistance or not.

Avoidance of Virolysis by Incorporating Complement System Regulatory Proteins: 

Viruses avoid complement by incorporating complement regulatory proteins into their envelope (i.e., HIV), producing proteins that structurally mimic complement regulator proteins or produce proteins that do not possess structural homology to complement recognition proteins but possess similar functional property. For example, Vaccinia virus secretes vaccinia complement control protein (VCP), a complement inhibitor whose amino acid sequence resembles host C4bBP, MCP and DAF. VCP blocks complement action at several stages of the pathway by binding to C4b or C3b.

Viruses have coopted aspects of the complement system to enhance infectivity. EBV and measles, for example, use two membrane proteins of the complement system, CD21 and CD46 as cellular receptors for attachment.

It is well established that many pathogenic enveloped viruses, including HIV-1, CMV, herpes virus, Ebola virus, and influenza virus, escape complement mediated virolysis by incorporating host cell complement regulatory proteins into their own viral envelope. The presence of complement regulators such as CD59 on the external surface of the viral envelope confers resistance to Ab dependent complement mediated lysis. This resistance to the lysis provides a likely explanation for the evidence that certain human pathogenic viruses are not neutralized by complement in human fluids even when they induce a strong Ab response. Inhibition of CD59 in the surface of either the viral envelope or the infected cell membrane sensitizes them to the lytic effect of complement (Hu, J Immunology, 2010, 184: 359-368). During maturation by budding, a number of enveloped viruses, such as human cytomegalovirus, HCMV, human T-cell leukemia virus type 1 (HTLV-1), HIV-1, simian immunodeficiency virus, Ebola virus, influenza virus and vaccinia virus capture CD59 and use it to evade the complement system (Stoiber, Mol. Immunol. 42: 153-160 (2005), Bernet, J Biosci 28: 249-264 (2003), Rautemaa, Immunology 106: 404-411 (2002), Nguyen, J Virol 74: 3264-3272 (2000) Saifuddin, J Exp. Med., 182: 501-509 1995), Spiller J Infect Dis 176: 339-347 (1997). Other viruses (e.g., Herpesvius saimiri) epxress a CD59 like molecule that aids the virus in avoiding the complement system.

Role of Cytokines:

–(IL-8): Studies in human volunteers have established an association between IL-8 and common cold symptoms, In rhinovirus infections there is a direct correlation between the severity of common cold symptoms and the concentration of IL-8 in the nasal secretion.

Role of Glycosylation:

Complex carbohydrates expressed by some pathogens facilitate the evasion of host immune responses and contribute to the destructive sequelae following infection. For example, the role of glycoproteins in HIV pathogenicity, particularly that of gp120, exemplifies the difficulty and important of complex carbohydrates in eliciting protective host immune responses. (Geng US2008/0038286).