Hantaviruses

Abstract

Hantaviruses (genus Hantavirus, family Bunyaviridae) are rodent- and insectivore-borne zoonotic viruses. Several hantaviruses are human pathogens, some with 10-35% mortality, and cause two diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Hantaviruses are enveloped and have a three-segmented, single-stranded, negative-sense RNA genome. The L gene encodes an RNA-dependent RNA polymerase, the M gene encodes two glycoproteins (Gn and Gc), and the S gene encodes a nucleocapsid protein. In addition, the S genes of some hantaviruses have an NSs open reading frame that can act as an interferon antagonist. Similarities between phylogenies have suggested ancient codivergence of the viruses and their hosts to many authors, but increasing evidence for frequent, recent host switching and local adaptation has led to questioning of this model. Infected rodents establish persistent infections with little or no effect on the host. Humans are infected from aerosols of rodent excreta, direct contact of broken skin or mucous membranes with infectious virus, or rodent bite. One hantavirus, Andes virus, is unique in that it is known to be transmitted from person-to-person. HFRS and HCPS, although primarily affecting kidneys and lungs, respectively, share a number of clinical features, such as capillary leakage, TNF-, and thrombocytopenia; notably, hemorrhages and alterations in renal function also occur in HCPS and cardiac and pulmonary involvement are not rare in HFRS. Of the four structural proteins, both in humoral and cellular immunity, the nucleocapsid protein appears to be the principal immunogen. Cytotoxic T-lymphocyte responses are seen in both HFRS and HCPS and may be important for both protective immunity and pathogenesis. Diagnosis is mainly based on detection of IgM antibodies although viral RNA (vRNA) may be readily, although not invariably, detected in blood, urine and saliva. For sero/genotyping neutralization tests/RNA sequencing are required. Formalin-inactivated vaccines have been widely used in China and Korea but not outside Asia. Hantaviruses are prime examples of emerging and re-emerging infections and, given the limited number of rodents and insectivores thus far studied, it is likely that many new hantaviruses will be detected in the near future.