It was demonstrated in the 1950s that the culture medium bathing virus infected cell lines could inhibit 
the multiplication of viruses in separate flasks. The active substances, termed interferons, are cytokines 
(as discussed above) and are produced within hours of virus infection to limit the spread of virus in the 
host whilst specific immune responses are developing. Most cell types can synthesise interferon but they 
can be grouped into three broad types according to the cell type that manufactures them. 
•  IFN- (alpha): leucocyte interferon,IFN- (beta): fibroblast interferon, 
•  IFN- (delta): immune interferon (activated T-lymphocytes and NK cells). 
Double-stranded RNA is the most potent stimulus for the production and release of interferon alpha and 
beta which act to prevent or limit the surrounding cells from becoming infected. Interferons are 
prophylactic rather than curative. The actions of interferons are somewhat varied in that they can 
modulate the activity of immune cells as well as induce resistance to viral infection. Two important 
antiviral processes induced by interferon in virus-infected cells are: 
•  the inhibition of viral-induced protein synthesis, and 
•  degradation of viral mRNA and rRNA. 
The central player in cells stimulated by IFN is protein kinase R(PKR). The letter R is taken from the 
viral dsRNA that activates the transcription of this protein kinase. PKR produced by cells stimulated by 
IFN inhibits viral driven protein synthesis by binding to the double-stranded RNA. PKR will also trigger 

apoptosis, presumably as a last resort following uncontrolled viral replication.

Controlled cell death (apoptosis) is a mechanism by which multicellular organisms remove unwanted 

cells either during development (wonderfully illustrated by the loss of the tail in the developing tadpole) or respond to genomic abnormalities (pre-cancerous changes). 
Apoptosis is also of great value as a defence mechanism against virus infection in cells. Apoptosis, in 
contrast to necrosis, is a tightly controlled process that leaves no mess and causes no damage to 
surrounding cells. As with host cell nucleases, viruses have acquired mechanisms with which to 
counteract the triggering of apoptosis. 

To what extent does the replication of the virus in the tissue cause the disease? Some of these help explain why virus infections can cause cell damage. For example, lytic infections will result in the loss of function of the infected cells. If sufficient numbers of cells are damaged in this way then the function of the organ may 
be compromised. Rotaviruses cause diarrhoea in humans and animals. The infected cells of the villi of 
the ileum are shed resulting in the loss of absorptive surface area contributing to the diarrhoea. The 
diarrhoea is a direct consequence of the viral damage in the enterocytes. Other examples of tissue 
damage are indirect. In true clinical poliomyelitis the virus damages the nerve cells that serve the muscle 
cells of the limbs. The damage to the nerve cells by the virus causes the muscle to atrophy. Virus cannot 
be found in the affected muscles themselves. Furthermore, poliomyelitis virus normally only multiplies 
within the enterocytes of the small intestine and they show no morphological alterations. This serves to 
remind us that the CPE observed in the cell lines used to grow viruses in the laboratory are not 
necessarily reflected in the natural host cells. 
The common symptoms of many viral infections, myalgia and headache, are usually indirect 
consequences of the host immune response (often cytokines such as tumour necrosis factors) 
rather than direct viral replication in the muscles and brain. 
Different infection strategies are employed by different viruses. The extremes are an acute, hit-and-run 
approach or a chronic persistent type of infection. Viruses choosing the former option will have less 
concern for the effects of rapid viral multiplication on the host. Such viruses will tend to suppress or 
inactivate acute (innate) mechanisms of host defence so as to gain time for the rapid multiplication of 
new virus. If the host is fatally damaged by the infection, as long as sufficient virus has been 
manufactured such that the infection is transmitted to new hosts, then the death of the host is of no 
concern. Aggressive virus multiplication will probably result in protective immunity such that, if the 
host recovers, he or she will not be available for the virus to reinfect. Chronic infections will need to 
adopt those strategies that deal with the longer term problems of specific immunity, i.e. the development 
of specific antibodies and cell-mediated cytotoxicity. The reaction of the host to intracellular parasites, viruses in particular, will often result in tissue damage.

In tissues with rapid turnover, virus-infected cells that are lost may be replaced (e.g. intestinal and skin 
epithelia). In non-replicating tissues like the heart and nerve tissue virus-infected cells cannot be lost so 
readily without possible functional deficit. If, therefore, the immune response damages these cells, the 
organ suffers from impaired function. Hepatitis viruses do not cause lytic infections of the hepatocyte 
but instead evoke a lymphocytic cell inflammation. This cell-mediated host response is what damages 

the liver tissue with resulting impairment of function. 

Immune complex reactions are typical of persistent infections. The antigen–antibody complexes can get 

stuck (‘deposit’ themselves) in arteries to cause vasculitis (which manifests itself as a skin rash) or in the basement membrane of the glomeruli to cause kidney damage. Both are seen with chronic hepatitis B infections. 

Cited By Kamal Singh Khadka
Msc Microbiology, TU.
Assistant Professor in PU, PBPC, PNC, LA, NA.
Pokhara, Nepal.

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