Physiological regulators

As mentioned above, infections with many hantaviruses and some arenaviruses are more frequent in male mice, and seroconversions are generally more frequent in the breeding season. Transmission of virus within host populations is also greater under more crowded conditions [16, 29, 31]. As explained above, these characteristics are due, at least in part, to behavioral factors. On the other hand, evidence is accumulating that physiological mechanisms might also contribute to this pattern of infection. Stress, associated with crowding, has been associated with immunosuppression in many animals, including some hantavirus host species (Microtus, Rattus, Clethrionomys glareolus) [11, 13, 24]. Increases in sex hormones, especially testosterone and corticosterone, have been clearly associated with immunosuppression in several species [2, 42]. Finally, the balance between type A and type B response to infection with Machupo virus was dose dependent [22]. It stands to reason, therefore, that the frequency of transmission and infection also might vary according to the degree of immunosuppression of the host.

Above, I suggested that the correlation between scars and infection status in hantavirus and arenavirus host rodents means that aggression leads to infection. Recent evidence suggests, however, that the cause and effect relationship between aggression and infection may not be as simple as it appears. Klein et al. [23] showed that male rats in the chronic stage of infection with Seoul virus were more likely to attack intruders and they spent more time fighting with them than did uninfected males. Furthermore, aggressive males had more virus in tissues (including testes and adrenal glands) than did less aggressive males.

Many other physiological factors may be related to viral infection, viral shedding, and viral persistence. These include those related to social interactions, nutrition, environmental conditions (e.g., temperature and rainfall), intake of plant secondary chemicals, and even the pH or presence of protein in the urine (which may be influenced by diet). Our knowledge of these potential relationships is scant.

In summary, regulators of viral infection in natural hosts are numerous. Most of these regulators have been inadequately studied and remain poorly understood. These regulators do not act independently; their total effect varies according to their interactions with other regulators. Nevertheless continued research and improved understanding of these regulators is important. The better we understand these regulators, the better we will be able to predict changes in disease risk to human populations, develop effective intervention programs, and appropriately and most efficiently target these intervention efforts.

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