February 2010

Until now, we have concerned ourselves with the molecular details of how viruses replicate in our cells to produce hundreds of progeny per cell. Now we will broaden our view to take account of the fact that these repeated rounds of virus replication are occurring in a body made up of about a hundred trillion cells, including an elaborate immune system that tries to fight off the infection.

Virus infection in vertebrates results in two general types of immune response. The first is a rapid-onset "innate" response against the virus, which involves the synthesis of proteins called interferons and the stimulation of "natural killer" lymphocytes. In some cases, the innate response may be enough to prevent a large scale infection. However, if the infection proceeds beyond the first few rounds of viral replication, the "adaptive immune response", kicks into high gear. The adaptive immune response itself has two components, the humoral response (the synthesis of virus-specific antibodies by B lymphocytes) and the cell-mediated response (the synthesis of specific cytotoxic T lymphocytes that kill infected cells). Both of these components of the adaptive immune response result also in the production of long-lived "memory cells" that allow for a much more rapid response (i.e., immunity) to a subsequent infection with the same virus.


1. How can we classify viral infections by 'outcome of the immune response'?

We can roughly establish four categories of virus infection based on what happens to the host (not including sub-clinical, inapparent infections).

Category 1 includes all cases for which the person gets sick and then either dies or recovers completely, with the elimination of all virus from the body. For categories 2-4, the initial infection may be acute or inapparent, but the body's immune response does not clear the virus completely, and things proceed to one of these situations, where there may be very little ("latent"), some ("chronic/persistent"), or abundant ("progressive") virus replication going on during the rest of the person's life. There is some overlap and ambiguity in these terms, but they are useful categorizations nonetheless.

2. After recovery from an acute viral infection, a person is usually "immune" to getting the same viral disease for years (perhaps a lifetime). What, then, is the explanation for the fact that we remain susceptible to getting a rhinovirus-caused "cold" throughout our lifetime?

There are over 100 different "serotypes" of rhinoviruses (and a smaller number of coronaviruses and adenoviruses) that all cause upper respiratory infections. When we get infected with one of these, our immune system responds and clears the virus from the body within a couple of weeks. The immune response also leaves us with a supply of specific "memory cells" that prevent that same virus from causing a clinically significant infection in us for years. But....., there are all of those other related viruses that can still infect us. For example, although all of the rhinoviruses are similar, their surface proteins are different enough such that the memory cells made during a previous immune response against, say, rhinovirus #36 will most likely not provide immunity to rhinovirus #24. So, at any time we are somewhat susceptible to whatever rhinoviruses we have not been infected by previously. (And, for older people, it's probably possible to get a cold from the same rhinovirus a couple decades apart.)

An update on the 100 or so rhinovirus serotypes was provided in a 2006 article in Journal of General Virology by Laine et al titled "Alignment of capsid protein VP1 sequences of all human rhinovirus prototype strains: conserved motifs and functional domains."

3. What is the basic understanding of the human adaptive immune response we need in order to progress with our study of virology?

The basics of B and T cell clonal selection and the various cellular interactions involved in the humoral and cell-mediated immune responses are the foundation knowledge of immunology needed for proceeding further in a study of virology. It is during the early stages of the clonal selection process that immunoglobulin gene DNA rearrangements occur. (Remember this? We covered it in BIOS 115 ).

As shown in this overview figure, initial antigen presentation by "Antigen Presenting Cells" leads to the activation and proliferation of TH cells, which are required for the generation of the humoral response (clonally-selected B cells secreting antigen-specific antibody that binds to extracellular virus particles) and the cell-mediated response (clonally-selected TC cells recognizing antigen-displaying "altered self" (i.e., infected) cells and killing them). A subset of these B and TC cell populations become antigen-specific "memory" cells to provide long-lived immunity to re-infection.