Viruses initiate infection and may cause disease through many defined stages. These include (a) entry into the body, (b) initia-tion of infection at a primary site (infection of the target tissue),c) replication of virus (Fig. 51-1) and spread to secondary site, and (d) manifestations of the disease.
Entry of the viruses into the body is the first step of viral infections. The skin is the best barrier to infections. In addi-tion to the skin, mucus, ciliated epithelium, gastric acid, bile, tears, etc. confer basic natural protection against many viruses. The viruses enter the body through the respiratory tract, skin, conjunctiva, alimentary tract, and genital tract to initiate the infection by breaking these natural barriers to infection.
Many viral infections are caused by entry of virus through the respiratory tract. The viruses enter the respiratory tract by droplets containing the viruses expelled from the nose and mouth of infected individuals during the act of coughing, sneezing, or talking.
· Some viruses, after entry into body, are confined to the respiratory tract where they multiply and produce local dis-eases. These are known as respiratory viruses. Examples of these viruses are influenza virus, respiratory syncytial virus, rhinovirus, coronavirus, adenovirus, and Coxsackie virus A.
· Other viruses after entry, initially multiply at the site of respiratory tract followed by hematogenous or lymphatic spread to other sites of the body. At these sites, the viruses replicate in large numbers and cause systemic manifesta-tions of the disease. The examples of such viruses include measles, mumps, rubella, varicella zoster, cytomegalovirus, and Epstein–Barr virus.
Many viruses enter the skin through abrasions or breaks in the skin. Molluscum contagiosum, cowpox, vaccinia, and vari-ola viruses enter the skin through minor lesions and produce cutaneous lesions at the site of entry. Other viruses, such as papilloma virus, enter the skin through minor injuries on the surface of skin, arboviruses by bite of insects, rabies virus by the bite of dogs and other animals, and hepatitis B virus and human immunodeficiency virus (HIV) by injection.
Some viruses may enter through the conjunctiva and may cause the disease. For example, adenovirus causes local mani-festations and measles virus causes systemic manifestation of the disease by entering through the conjunctiva.
The viruses also cause infection by entering through the alimentary tract, which is another important route of infec-tion by viruses. The viruses, such as rotaviruses, enteroviruses, adenoviruses, reoviruses, hepatitis viruses, and other gastro-intestinal viruses cause infections of the gastrointestinal tract and produce disease.
Rotaviruses, on ingestion, are carried to the intestinal tract in which they initiate the infection. Rotavirus is restricted to the gut, producing a local disease. Other viruses, such as enteroviruses, adenoviruses, reoviruses, and hepatitis viruses, on the other hand, initiate infections through the alimentary tract, replicate locally, and then are transported to other sites for subsequent replication and spread to target tissues, produc-ing systemic manifestations of the diseases.
Natural barriers against viral infections include (a) the acidity of the stomach, (b) the alkalinity of the small intestine, and (c) secretory enzymes found in the saliva and pancreatic secretions. Intestinal mucus and secretory IgA antibodies are important and offer partial protection to the intestinal tract. Enveloped viruses usually fail to establish infection in the gastrointestinal tract, because these are destroyed by bile secreted in the gastrointestinal tract.
Viruses are also transmitted through sexual contact and enter the body through the genital tract.
· HIV, hepatitis B virus, and hepatitis C virus are sexually transmitted and do not produce any local lesions in the genital tract but produce systemic manifestations.
· Papilloma viruses and herpes simplex viruses (HSVs) are also transmitted sexually and produce lesions locally in the genital tract and perineum.
Few viruses may cause congenital infection in fetus in utero being transmitted from the infected mother. Rubella and cytomegaloviruses are the viruses that are more commonly associated with congenital infections. Depending upon the age of the fetus, these viruses may cause malformations or even fetal death and abortion.
The viruses, on entry into the human host, may remain at the primary site of infection, replicate, and cause infection of the target tissue. The specificity of the virus-attachment proteins and tissue-specific expression of receptors during replication are two important properties of viruses to cause infection of target tissues.
The viruses are spread in the body mainly by the blood stream and the lymphatic system. Transport of virus in the blood is known as viremia. After multiplication in the lymph nodes, the virus enters the blood stream, resulting in primary viremia. In the blood stream, the virus may exist either free in the plasma or it may be ingested by the lymphocytes or macrophages. In macrophages, the viruses may die or replicate or may be car-ried by the mononuclear phagocytic system to the spleen and liver. Replication of the viruses in macrophages, in the endo-thelial lining of blood vessels, or in the spleen and liver results in production of viruses in large numbers. This leads to mas-sive spillover of the virus into the blood stream, causing sec-ondary viremia. This heralds the onset of clinical symptomsof viral infections including the prodromal phase in eruptive fever. Subsequently, it is carried by blood stream to reach target organs (skin, brain, liver, etc.) in which the viruses replicate producing characteristic distinctive lesions.
Viruses enter the brain or central nervous system (a) through the blood stream, (b) through the infected cerebrospinal fluid or meninges, and/or (c) through the infection of the peripheral and sensory (olfactory) neurons.
The clinical manifestations of viral diseases depend on the complex interaction of virus and host factors. The outcome of the infection, that is, the disease manifestation depends on the:
· Age, general health, and immune status of the person,
· Dose of the infective virus, and
· Genetics of the host and the virus. After the host is infected by the virus, the immune status of the host plays an impor-tant role and determines the outcome of viral infection whether it will be an asymptomatic infection, a benign disease, or a life-threatening disease.