Hantavirus Species Research Articles

Hantaviruses. a short review.

Hantaviruses are rodent viruses that have been identified as etiologic agents of 2 diseases of humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). This article presents a concise review of hantavirus biology, the medical features of HFRS and HPS, and tests for the detection of hantavirus infections in humans. Hemorrhagic fever with renal syndrome is a disease found outside the Americas and denotes a group of clinically similar illnesses that vary in severity relative to the causative agent. Hantavirus pulmonary syndrome is associated with higher mortality than HFRS, was first recognized as a hantavirus disease in 1993, and occurs within the American continents. Recent genetic studies show that both Old and New World hantavirus species coevolved with specific rodent hosts. The list of distinct hantaviruses associated with HPS is growing. The burgeoning human population is causing disruption of natural habitats as more and more land is cleared for commercial and residential purposes. Many rodents readily adapt to life in human settlements, where they generally benefit from reduced predation and where they sometimes proliferate to high numbers. Although often referred to as emerging pathogens, HPS-associated hantaviruses emerge through increased exposure of humans to rodents and their excreta, not through genetic drift or reassortment of the viral genome. Based on current human population growth and development trends, hantavirus diseases will become more common in the near future unless public health measures are taken to curtail or eliminate rodents from human communities.

Hantaviruses A Short Review

○ Objective.-Hantaviruses are rodent viruses that have been identified as etiologic agents of 2 diseases of humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). This article presents a concise review of hantavirus biology, the medical features of HFRS and HPS, and tests for the detection of hantavirus infections in humans. Data Synthesis.-Hemorrhagic fever with renal syndrome is a disease found outside the Americas and denotes a group of clinically similar illnesses that vary in severity relative to the causative agent. Hantavirus pulmonary syndrome is associated with higher mortality than HFRS, was first recognized as a hantavirus disease in 1993, and occurs within the American continents. Recent genetic studies show that both Old and New World hantavirus species co-evolved with specific rodent hosts. The list of distinct hantaviruses associated with HPS is growing. The burgeoning human population is causing disruption of natural habitats as more and more land is cleared for commercial and residential purposes. Many rodents readily adapt to life in human settlements, where they generally benefit from reduced predation and where they sometimes proliferate to high numbers. Conclusions.-Although often referred to as emerging pathogens, HPS-associated hantaviruses emerge through increased exposure of humans to rodents and their excreta, not through genetic drift or reassortment of the viral genome. Based on current human population growth and development trends, hantavirus diseases will become more common in the near future unless public health measures are taken to curtail or eliminate rodents from human communities.

Molecular epidemiology of viral pathogens and tracing of transmission routes: hepatitis-, calici- and hantaviruses.

The need to rapidly identify new therapeutic drugs and vaccines for clinically important viral infections has resulted in intensive study of the molecular properties of viruses. Modern molecular techniques have provided tools for tracing infections and studying the evolution of viruses. OBJECTIVE STUDY AND DESIGN: Two examples illustrating how modern molecular techniques can be used in clinical virology and molecular epidemiology (hepatitis and caliciviruses), and one example documenting their importance in basic research (hantaviruses) will be discussed. Water- and food-borne outbreaks caused by the faeco-orally spread hepatitis A virus (HAV) are common in areas lacking proper sanitation, but they are possible also in countries with low seroprevalence. In water epidemics, the sequence comparisons between the virus from patients and from water have been used successfully. Hepatitis B virus variants are clinically important and challenge the diagnostic tests and prophylactic measures. Some hepatitis C (HCV) genotypes appear to be associated with more severe pathology and others respond better to antiviral treatment. Nosocomial and occupational infections are not rare, and the source can be identified by phylogenetic analysis of nucleotide sequences obtained from the infected individuals. The overwhelming role of Norwalk-like caliciviruses (NLV) in adult diarrhoea and especially in food- and water-borne epidemics has become apparent during the last decade. Methods are under development for detecting these viruses, not only from patient samples and water, but also from other environmental samples (e.g. foodstuff and surface swabs). The analysis of the genetic variation and evolution of the Old World hantaviruses in their carrier rodents has shown that the extent of genetic diversity correlates with geographical distance. As a rule, phylogenetic relationships of hantaviruses resemble those of their rodent hosts, suggesting virus-host co-evolution. Exceptional host-switch events allow a study on still radiating hantavirus species. There is suggestive evidence that natural reassortant hantaviruses are involved in human infection.

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species

In central Europe, hemorrhagic fevers with renal syndrome (HFRS) in humans are caused by the hantavirus species Puumala (transmitted by voles) and a second, Hantaan-related species (transmitted by mice). The second virus could be identified as Dobrava virus. To date, 19 clinical cases of Dobrava infection have been found in Germany and Slovakia. All patients exhibited a mild/moderate clinical course and no case fatality occurred. Screening for infected rodents revealed that the striped field mouse (Apodemus agrarius) represents the main reservoir for Dobrava virus in central Europe. Nucleotide sequence comparisons and phylogenetic analysis based on complete and partial genomic S segment nucleotide sequences placed the Slovakian A. agrarius-derived hantavirus strains within the Dobrava species, forming a cluster on the Dobrava phylogenetic tree. In east Slovakia, a single Dobrava virus-infected yellow-necked mouse (Apodemus flavicollis) was trapped in a locality that predominantly showed Dobrava-infected A. agrarius. Comparison of the S segment sequence (nucleotides 381-935) revealed that the Dobrava strain from A. flavicollis shows only 84.3% nucleotide homology to A. agrarius-derived strains from this location but 96.3% homology to A. flavicollis-derived Dobrava strains from the Balkans (southeast Europe). Phylogenetic analysis of the partial S segment placed the A. flavicollis-derived Dobrava strain from Slovakia on a distinct Dobrava lineage (DOB-Af) together with the south-east European A. flavicollis-derived strains. The results indicate that Dobrava strains from A. agrarius (DOB-Aa) vs. A. flavicollis (DOB-Af) could develop different degrees of virulence in humans.

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species

In central Europe, hemorrhagic fevers with renal syndrome (HFRS) in humans are caused by the hantavirus species Puumala (transmitted by voles) and a second, Hantaan-related species (transmitted by mice). The second virus could be identified as Dobrava virus. To date, 19 clinical cases of Dobrava infection have been found in Germany and Slovakia. All patients exhibited a mild/moderate clinical course and no case fatality occurred. Screening for infected rodents revealed that the striped field mouse (Apodemus agrarius) represents the main reservoir for Dobrava virus in central Europe. Nucleotide sequence comparisons and phylogenetic analysis based on complete and partial genomic S segment nucleotide sequences placed the Slovakian A. agrarius-derived hantavirus strains within the Dobrava species, forming a cluster on the Dobrava phylogenetic tree. In east Slovakia, a single Dobrava virus-infected yellow-necked mouse (Apodemus flavicollis) was trapped in a locality that predominantly showed Dobrava-infected A. agrarius. Comparison of the S segment sequence (nucleotides 381–935) revealed that the Dobrava strain from A. flavicollis shows only 84.3% nucleotide homology to A. agrarius-derived strains from this location but 96.3% homology to A. flavicollis-derived Dobrava strains from the Balkans (southeast Europe). Phylogenetic analysis of the partial S segment placed the A. flavicollis-derived Dobrava strain from Slovakia on a distinct Dobrava lineage (DOB-Af) together with the south-east European A. flavicollis-derived strains. The results indicate that Dobrava strains from A. agrarius (DOB-Aa) vs. A. flavicollis (DOB-Af) could develop different degrees of virulence in humans. J. Med. Virol. 63:158–167, 2001. © 2001 Wiley-Liss, Inc.

Hantavirus infections in Europe

Publisher Summary This chapter provides an overview of the epidemiology of hantavirus infections in Europe and the genetics of European hantaviruses. Hantaviruses form a separate genus within the family Bunyaviridae . Unlike other members of the family, hantaviruses are not arthropode-borne agents. They are maintained in persistently infected rodent hosts but are not transmitted by any insect vectors and seem to coevolve with their natural hosts; each hantavirus species being predominantly associated with one specific rodent species. This results in the circulation of distinct hantaviruses on different continents and in the geographical clustering of hantavirus genetic variants. When transmitted to humans, pathogenic hantaviruses from Eurasia, which are carried by Murinae or Arvicolinae rodents of the Muridae family, can cause hemorrhagic fever with renal syndrome while most of their relatives from the Americas, which are maintained in indigenous Sigmodontinae rodents of the Muridae family, can cause hantavirus pulmonary syndrome. During recent years, knowledge of the distribution and significance of hantaviruses in Europe has been increasing rapidly. Several outbreaks caused by Puumala hantavirus, known previously as a pathogen almost exclusively in Scandinavia, Russia, and the Balkans, have been registered in Germany and Belgium.

Virus evolution and genetic diversity of hantaviruses and their rodent hosts.

Unlike other members of the Bunyaviridae family, which must be regarded as arboviruses1, hantaviruses are not transmitted by arthropod vectors, and are exclusively maintained in the populations of their specific rodent hosts. Thus, the prefix “Robo” (from ROdent-BOrne) seems to be more appropriate for the viruses constituting the genus Hantavirus 2. Each of the over 20 currently recognized hantavirus species is predominantly associated with one (or a few closely related) specific rodent species in which it establishes persistent infection. The fact that rodents, or more specifically, rodents alone, constitute the entire host range within which hantaviruses evolve, has several important consequences: (a) Distinctive characteristics of different hantaviruses are formed as adaptations to the distinct genetic environment of their rodent hosts; (b) Contemporary distribution of distinct hantaviruses reflects complicated history of co-speciation events and rodents’ migrations (the most recent extensive rodent migrations were caused by the sequence of several glaciation and deglaciation events in the northern hemisphere). This forms a basis for the circulation of distinct hantaviruses on different continents, their co-existence in some geographic regions, and geographical clustering of hantavirus genetic variants; (c) As a general rule, humans are merely evolutionary “dead-end” hosts for hantaviruses, and thus, human epidemics do not contribute to virus evolutionary process3. As humans are usually naive towards hantaviruses as antigens, that results in sometime dramatic immunological “excesses” leading to high mortality of known hantavirus-caused diseases, severe hemorrhagic fever with renal syndrome (HFRS) (up to 10–12%) and hantavirus pulmonary syndrome (HPS) (up to 40–50%).

Person-to-Person Transmission of Hantavirus?

An outbreak of hantavirus pulmonary syndrome (HPS) in southern Argentina last fall that killed 11 of the 20 people infected may have featured the first known cases of person-to-person transmission of the disease. Although many hantavirus species have been identified and found to cause illness in humans, extensive epidemiologic studies had failed to turn up any clear-cut evidence of transmission between infected people. Experts previously believed that the primary means by which humans contracted hantavirus infections, which are known to attack the lungs or kidneys, was inhalation of tiny particles of the fecal droppings of infected rodents. Now, however, a team of Argentine and US researchers investigating the 1996 Argentine outbreak has found epidemiologic evidence that strongly suggests person-to-person transmission ( Emerg Infect Dis. 1997;3:171-174). The outbreak, which began last September among residents or visitors of 3 towns in southern Argentina, later involved individuals who'd had contact with infected patients but

Hantaviruses: clinical, microbiologic, and epidemiologic aspects.

Hantaviruses comprise a genus of the family Bunyaviridae. Bunyaviruses are enveloped viruses with a negative-sense, tripartite RNA genome. Hantaviruses are etiologic agents for two acute and severe illnesses of man, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Each hantavirus is primarily associated with a single rodent host species or genus, and is transmitted to man through accidental inhalation or ingestion of virus-contaminated rodent excreta. The distribution of hantaviruses is worldwide. HFRS is caused by infection with Hantaan, Seoul, Dobrava/Belgrade, and Puumala hantaviruses, all of which are enzootic in murid rodents of Old World origin. HPS is caused by any of several hantavirus species associated with indigenous New World rodents of the subfamily Sigmodontinae, family Muridae. HFRS and HPS have numerous common epidemiologic, clinical, and laboratory characteristics. Common features include fever, myalgia, thrombocytopenia, neutrophilia, and a profound capillary leak syndrome associated with hypotension, decreased cardiac output, and shock. Worldwide, HPS is much less common than HFRS but is associated with a higher mortality rate. Recovery from hantavirus disease is generally complete, although chronic renal insufficiency may be a rare sequel of HFRS.

Hantavirus in the southwestern United States: Epidemiology of an emerging pathogen

In May of this year, an outbreak of sudden, unexplained, and highly fatal respiratory illness of unknown etiology was identified in the four-corners region of the southwestern United States. Within 3 weeks after the collaborative response launched by the state and local health agencies in the affected area, laboratory studies from the federal Centers for Disease Control and Prevention suggested that an acute infection with a previously unrecognized Hantavirus species was responsible for the reported cluster of cases. The hantavirus associated with this outbreak has since been isolated in tissue culture, and diagnostic test systems specific for the newly identified hantavirus have been developed. This article summarizes the history of the outbreak as experienced by investigators from the Arizona Department of Health Services and reviews the epidemiologic and clinical aspects of both the current epidemic and hantaviruses in general. The sudden occurrence of acute illnesses in the Southwest due to a previously unrecognized hantavirus reaffirms that the potential for the emergence of new infectious diseases exists at any place or time in the United States. The response to the outbreak also illustrates how community clinicians and federal, state, and local health agencies work together to promptly identify the emergence of new disease threats, rapidly determine new etiologic agents, and develop and swiftly implement appropriate disease prevention and control strategies.