Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture

Hantaviruses are enzootic viruses that maintain persistent infections in their rodent hosts without apparent disease symptoms. The spillover of these viruses to humans can lead to one of two serious illnesses, hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and natural history of these viruses following an increase in the number of outbreaks in the Americas. In this review, current concepts regarding the ecology of and disease associated with these serious human pathogens are presented. Priorities for future research suggest an integration of the ecology and evolution of these and other host-virus ecosystems through modeling and hypothesis-driven research with the risk of emergence, host switching/spillover, and disease transmission to humans.

One of the most fundamental questions in immunology pertains to the recognition of non-self, which for the most part means microbes. How do we initially realize that we have been inoculated with microbes, and how is the immune response ignited? Genetic studies have made important inroads into this question during the past decade, and we now know that in mammals, a relatively small number of receptors operate to detect signature molecules that herald infection. One or more of these signature molecules are displayed by almost all microbes. These receptors and the signals they initiate have been studied in depth by random germline mutagenesis and positional cloning (forward genetics). Herein is a concise description of what has been learned about the Toll-like receptors, which play an essential part in the perception of microbes and shape the complex host responses that occur during infection.

This review discusses the control exerted by natural CD4(+) CD25(+) regulatory T cells (natural T(reg) cells) during infectious processes. Natural T(reg) cells may limit the magnitude of effector responses, which may result in failure to adequately control infection. However, natural T(reg) cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses. We describe here various situations in which the balance between natural T(reg) cells and effector immune functions influences the outcome of infection and discuss how manipulating this equilibrium might be exploited therapeutically.