Serological, molecular biological and tissue culture methods are used to diagnose viral infections and to accertain the extent of viral damage and the quality and intensity of the body's immune response.

The antibody response to a viral infection normally starts with the relatively transient production of IgM followed by a long lasting production of IgG. For this reason, a specific IgM antibody response can generally be taken as a sign of early infection. The serological detection of free viral antigen can precede the earliest serological response and this type of assay can be useful for certain infections, e.g. parvovirus B19, HIV, hepatitis B virus (HBV) and human herpesvirus-6 (HHV-6). Antigen assays can also be used to distinguish persisting infection, in spite of IgG response, from a cured infection. Again, this type of approach has been employed with HIV and HHV-6.

The quality and intensity of the anti-viral cellular immune responses can be assessed using lymphocyte subset analyses, natural killer cell mediated cytotoxicity, and measurements of cytokine production including IL2, IL4, interferon, etc.

For some infections, actual culture of the virus can provide conclusive evidence of active infection, as well as the isolate for susceptibility studies. Active infection can also be inferred from the results of molecular probe based assays, including the use of polymerase chain reaction and branched DNA procedures.

Individuals can harbor multiple viral infections which may potentiate each other and lead to atypical manifestations.

The extent of organ damage can be assessed directly using tissue biopsies, or measured indirectly by assaying for various components released from the infected organ. For example 14-3-3 protein in Creutzfeldt-Jakob disease.

Finally, sequential measurements can provide a means to determine natural outcome as well as response to specific intervention.