Viruses need the cell machinery in order to produce their own proteins. They are intracellular parasites that can only replicate inside cells. Viruses usually are made of very simple structures, consisting of proteins and nucleic acid, even though their structure and composition is quite variable.They fall into two distinct groups, depending on their nucleic acid: DNA and RNA viruses. They are grouped in different families by their morphology and structure.   

Photograph showing the African Swine Fever virus. Electronic microscopy. 

MAIN VIRAL DISEASES OF THE PIG.

(sc): single chain. (dc): double chain.

From an immunological point of view, it is important to know the different immune mechanisms that can act against the viral particle through the viral replication cycle, the infected cells, or both.  (1.) Usually, the viral replication cycle begins with the binding of the virus (free virus) to the host cell through specific receptors (adsorption). These receptors determine the tropism and specifity: viruses cannot infect just any cell or any species, because they have specific tropism. (2).Once inside the cell, the virus looses its envelope and this allows the viral genome to enter the cell (liberation). Then, the process of viral replication starts.   

During this stage, the synthesis of cellular proteins is inhibited and only the genetic information of the virus will be processed. The mechanisms of this phase depend on the type of virus (DNA or RNA). (3.) When the virus is DNA a replication takes place which produces new viral DNA. (4.) This new DNA is transcribed (transcription) into RNA (blue), which will be synthesized, by a translation process into different viral proteins that will later be assembled into virus particles. In the case of RNA viruses, transcription is not necessary, so new viral proteins are directly synthesized from the viral RNA. This mechanism of RNA replication is different for retroviruses: by means of the reverse transcriptase, viral DNA is produced and is later integrated into host DNA.  The next steps  (replication, etc.) take place from this integrated DNA. 

Diagram of the viral replication cycle. (1) adsorption. (2) liberation. (3) replication. (4) assembling and viral liberation. 

Different immunological mechanisms against viral particles (antibodies, cytokines, complement) or against infected cells (NK, CD 8, ADCC, complement)

viral replication cycle

In most viral infections, the immune system has the opportunity of attacking viral particles in some stages of the infection (before viruses enter cells or when they are liberated after their replication). It may also  take place in infected cells during the protein production or viral assembling phase. During these stages, antigens that appear in the membrane of the infected cell can activate the immune response.. In some cases, such as endogen porcine retroviruses (three different types have been described: A, B, B1 and C) or herpes viruses (Aujeszky´s disease), infection can last for long periods of time without the presence of any viral  particles or surface antigens being expressed in the membrane of  infected cells. When this happens, the immune system is unable to fight the infection, because there are not viral peptides to flag its presence. But eventually infection is reactivated (causes are not yet well known) and new infectious virions are liberated.   

From the immunological  point of view viral infections can be fought once the virus has crossed the mechanical-chemical barriers. This is done by targeting viral particles (virion), infected cells or both. Different mechanisms of natural and adaptive immunity are used against these infections.

Innate response against viruses

The most effective mechanisms of the innate response against viral infections are mediated by interferon and by the activation of NK cells. These mechanisms are mainly aimed against infected cells.

Interferon is a cytokine with three different types: a, b and g. The first two are mainly produced by monocytes-macrophages and to a lesser extent by fibroblasts. However,  interferon-g is produced by CD 4 and CD 8 lymphocytes and NK cells. Interferon has a stong anti-viral action and promotes different mechanisms such as: transitory resistance of cells; induction of different molecules with anti-viral activity; activation of genes expressing anti-viral proteins, and increasing the expression of SLA I and SLA II.

Activation of genes that produce anti-viral proteins

 NK cell diagram.

NK cells are naturally activated against cells infected by viruses. The activation mechanism seems to be related to the alterations in the changes of the SLA in the infected cells. The reaction of NK cells against infected cells is not based on an antigenic basis (NK cells lack TcR). This cytotoxic mechanism is very effective in viral infections. 

Finally, the alternative pathway of complement activation also has the effect of very effectively activating  the destruction of the viral particle. 

Adaptive response against viruses.

Adaptive immunity acts against both viral particles and infected cells. The most important mechanisms against viral particles are antibodies; while the cytotoxic mechanisms are the most important against infected cells. This is mediated by cells (CD 8+), antibodies and cells (ADCC) or antibodies and the complement (classical pathway). 

Against  viral particle.

The viral capsid is made of proteins and therefore, it is very antigenic. It induces the production of a large number of antibodies that can have different actions against the virus: 
Neutralization of the infection (IgG, IgM and IgA), prevents the virus from entering the cells, 
Viral aglutination  (IgM), reduces the number of infectious agents.
Phagocytosis activation forms the antigen-antibody complex and stimulates the Fc receptor on macrophages.

Against infected cell. 

Cells infected by viruses can express on their membranes viral antigens long before the viral assembling takes place. Thus, their destruction is a very effective mechanism for avoiding the production of more viruses. The adaptive immune response attacks infected cells using antibodies (ADCC system, classical pathway of complement activation, phagocytosis) and cytotoxicity mechanisms mediated by CD 8+ lymphocytes. This is one of the most effective mechanisms against viral infections. 

Cytotoxic mechanism induced by CD 8 lymphocytes

Cytotoxic T lymphocytes 
© James A. Sullivan, Cells Alive!