The human immune system is a large and complex beast, but in general it has two roles. Firstly, to prevent an infection from causing any harm and secondly to protect the body against a repeat attack. For many diseases protection against reinfection happens very efficiently, and this is the principle on which vaccines are based. By exposing your body to a non-harmful sample of the disease your immune system can built up resistance. For cytomegalovirus however the immune system seems mysteriously unable to protect against reinfection, which is a major problem for the design and development of working vaccines.

Image from wikimedia commons by user Emmanuel Boutet

Cytomegalovirus (hereafter referred to as CMV which is easier to spell) is a type of herpes-virus that are often not deadly for healthy patients, but can be dangerous for people with a compromised immune system. It can cause massive problems in pregnancy and is one of the major causes of congenital diseases including childhood deafness and neurological disorders.

The first step in developing resistance against diseases is for cells that have visited the site of infectionto  ‘present’ a little bit of the virus (the antigen) to the T cells of the immune system. These T cells can both kill the virus wherever they encounter it again, and help to lay down the long term memory of the immune system. It is this antigen-presentation step that the CMV inhibits, by stopping the T cells from seeing them they remain essentially invisible to the cells of the immune system.

The antigen presenting cell is using the MHC complex to 'show' the T-cell a piece of virus. It can then become a helper cell, or a killer cell. Image from wikimedia commons.

CMV is a latent virus; like all herpesviruses it remains within the cells after a primary infection. Work done on rhesus macaque monkeys showed that the blocking of the immune system response allowed a second viral infection (called a superinfection). The success of the superinfection was dependant on the viral genes for knocking out antigen presentation, if these genes were knocked out the superinfection did not succed unless the monkeys being infected had a severe depletion in T cell numbers. (ref. 1) Humans are not the same as rhesus monkeys as the monkeys shed the virus at a higher rate, and show more frequent reinfection. However this pattern of high shedding and reinfection is often seen in perinatal cases of CMV, which means that the model is especially useful in this situation.

What all this means is that the conventional vaccine route does not work with CMV, as the infecting virus will stop the immune system mounting any kind of response. There are still options for protection, but they rely on B cells (which produce antibodies) rather than T cells. You might not be able to stop yourself getting the CMV, but if you have it (especially for pregnant or immunocompromised individuals) it might be possible to treat it with antibodies from another patient. Studies done observing pregnant women with CMV have shown that this can lead to a reduction in congenital infection (ref. 2).

An electron-microscope picture of a herpesvirus, showing the outer coat proteins. From wikimedia.

For viruses such as CMV, which evade conventional vaccine treatments, this kind of research is vital to explore alternative treatments. Despite differences in species the rhesus macaque model looks like a promising way to examine the affect of treatments on secondary infection particularly in the case of prenatal infection.

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Ref 1: Hansen, S., Powers, C., Richards, R., Ventura, A., Ford, J., Siess, D., Axthelm, M., Nelson, J., Jarvis, M., Picker, L., & Fruh, K. (2010). Evasion of CD8+ T Cells Is Critical for Superinfection by Cytomegalovirus Science, 328 (5974), 102-106 DOI: 10.1126/science.1185350

Ref 2: Nigro, G., Adler, S., La Torre, R., & Best, A. (2005). Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection New England Journal of Medicine, 353 (13), 1350-1362 DOI: 10.1056/NEJMoa043337