Hantaviruses Flashcards
Genus and family of hantaviruses
genus Orthohantavirus (“hantavirus”) is comprised of a group of more than 30 distinct species of rodent- and insectivore-borne viruses of the
family Hantaviridae
Bunyavirales order
Clinical syndromes of hanta
Two major forms of hantavirus disease are recognized, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS; also called HPS).
Among the agents of HCPS, the most severe forms are associated with Sin Nombre virus and the southern (prototypical) form of Andes virus; slightly milder forms are caused by the northern form of Andes virus (Andes-Nort), Laguna Negra virus, and Choclo virus. Rio Mamore virus and the closely related Maripa virus are emerging as agents of HCPS in South America [1-5].
The known etiologic agents for the more serious forms of HFRS are Hantaan virus and Dobrava virus; a form of intermediate severity is caused by Seoul virus, and a milder form of HFRS is caused by a vole-borne hantavirus, Puumala virus
Pathogenesis in hanta - receptor, tropism, pathology
CHRONIC disease: The possibility of a persistent state in humans has been raised by a study of immune responses in 78 patients with Andes virus infections in which both T cell and neutralizing antibody responses failed to decline in intensity during years of convalescence [10]. Viremia was not present in convalescent subjects, so the location of any long-term reservoir of Andes virus replication within the host, if present, is not known.
The hantaviruses show very similar tissue tropism in both human and rodent hosts, with consistent involvement of the vascular endothelium of the heart, kidney, lung, and lymphoid organs [11]. Involvement of the central nervous system is rare.
Neither rodent nor human infection leads to overt cytopathic damage by direct viral involvement, consistent with the pattern observed in most in vitro studies.
Cell entry — Hantaviruses use beta-3 integrins to enter endothelial cells, which leads to dysregulation of endothelial cell migration.
Cytokines — In HCPS, it is suspected that various proinflammatory and antiviral cytokines, such as TNF-alpha, IL-1 beta, and interferon (IFN)-gamma, are agents of a reversible increase in vascular permeability that leads to severe, noncardiogenic pulmonary edema
In the case of hemorrhagic fever with renal syndrome (HFRS), capillary leak is manifest in the retroperitoneum; the kidneys are heavy, edematous, and congested, weighing 50 to 100 percent more than expected
Hanta vector
All medically important hantaviruses are carried by rodents of the families Muridae and Cricetidae.
Hanta structure & Baltimore group
(-)ssRNA.
Divided into three segments. The L, or large, segment encodes the replicative enzymes, RNA-dependent RNA polymerase and endonuclease; the M (middle) segment encodes the envelope glycoproteins, Gn and Gc; and the S segment encodes the nucleocapsid protein, N
Baltimore: V
The envelope glycoproteins may mediate attachment to cells via the beta-3-integrin cell surface molecule, which is found on endothelial cells and platelets throughout the body
Hanta incubation & transmission
Rodent contact is an important factor in the transmission of hantaviruses to humans. Many hantaviruses are shed in the urine, feces, or saliva of acutely infected reservoir rodents. It is suspected that much, if not all, transmission to humans occurs via the aerosol route
Person-to-person transmission of hantaviruses is rare and has been confined only to a single hantavirus species, Andes virus.
Incubation: 1-6 weeks
Hanta diagnostics
Acute infection can be distinguished from remote (past) infection by the presence of specific anti-hantavirus IgM in the former (usually the nucleocapsid or N antigen is used) or a fourfold rise in titers of anti-hantavirus IgG.
viral RNA usually disappears from the circulation after a few days, and serologic techniques have high diagnostic accuracy. For the infections caused by Puumala virus, which typically causes mild infection, RNA can be detected in only a small minority of patients (usually those who have an unusually severe infection). For these reasons, few if any clinical laboratories offer a routine RT-PCR diagnostic test. RT-PCR is more useful as a backup or confirmatory diagnostic test or for identifying possible sites of infection
Hanta treatment
Supportive, ECMO
Ribavirin is a nucleoside analogue that is effective in hemorrhagic fever with renal syndrome due to Hantaan virus, a different strain of hantavirus [46]. A prospective, randomized, double-blind, placebo-controlled trial of 242 patients with serologically confirmed Hantaan virus in the People’s Republic of China found a sevenfold decrease in mortality among ribavirin-treated patients
Two patients with extremely severe Puumala virus infection were successfully treated with icatibant, a drug licensed for treatment of acute hereditary angioedema [23,109,110]. Icatibant acts as a selective antagonist of the bradykinin type 2 receptor, reverses increased vascular permeability, and inhibits vasodilatation
In China and Korea, killed-virus vaccines are available for Hantaan virus and/or Seoul virus [66], but their expense precludes their widespread usage in the most heavily affected regions of China. No vaccines are available for Sin Nombre virus or other agents of HCPS
