Family: Hantaviridae

Steven B. Bradfute, Charles H. Calisher, Boris Klempa, Jonas Klingström, Jens H. Kuhn, Lies Laenen, Nicole D. Tischler and Piet Maes

The citation for this ICTV Report chapter is the summary published as Bradfute et al. (2024):

ICTV Virus Taxonomy Profile: Hantaviridae, Journal of General Virology 2024, (in press)

Corresponding author: Piet Maes (piet.maes@kuleuven.be)
Edited by: Holly Hughes and Evelien Adriaenssens
Posted: March 2024

Summary

Hantaviridae is a family for negative-sense RNA viruses with genomes of about 10.5–14.6 kb (Table 1 Hantaviridae). The family includes seven genera (Actinovirus (subfamily Actantavirinae), Agnathovirus (subfamily Agantavirinae), Loanvirus, Mobatvirus, Orthohantavirus and Thottimvirus (subfamily Mammantavirinae), and Reptillovirus (subfamily Repantavirinae). These viruses are maintained in and/or transmitted by small mammals, but also by fish and reptiles. Several orthohantaviruses can infect humans, causing mild, severe, and sometimes-fatal diseases. Hantavirids produce enveloped virions containing three single-stranded RNA segments with open reading frames (ORFs) that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain.

Table 1 Hantaviridae. Characteristics of members of the family Hantaviridae.

* mostly based on experiments with mammalian orthohantaviruses

Viruses assigned to each of the seven genera form genus-specifc monophyletic clades based on phylogenetic analysis of concatenated L protein/RdRP, glycoprotein and N sequences. Viruses from all seven genera share one or more of the following characteristics: (i) enveloped pleomorphic virions; (ii) tri-segmented, negative-sense RNA genome without polyadenylated tracts at the 3′-end; (iii) genomic sequence complementarity at the 5′- and 3′-ends; and (iv) capped but not polyadenylated virus mRNAs (Maes et al., 2004).

Piscine Hosts

Genus Actinovirus. Viruses in this genus infect actinopterygian (lophiid, percid, ogcocephalid, and triacanthodid, and possibly goblid and melanotaeniid) fish.

Genus Agnathovirus. Viruses in this genus infect agnathan (myxinid) fish.

Mammalian Hosts

Genus Loanvirus. Viruses in this genus infect rhinolophid, verspertillionid, and possibly nycterid bats and possibly murid rodents.

Genus Mobatvirus. Viruses in this genus infect emballonurid, hipposiderid, pteropodid and possibly molossid, and vespertillionid bats and soricid and talpid eulipotyphla.

Genus Orthohantavirus. Viruses assigned to this genus infect soricid and talpid eulipotyphla and muroid and possibly dipodoid rodents.

Genus Thottimvirus. Viruses in this genus infect soricid and possibly talpid eulipotyphla.

Reptilian Hosts

Genus Reptillovirus. Viruses in this genus infect gekkonid and possibly scincid reptiles.

Virion

Morphology

Only known for members of the genus Orthohantavirus (see Orthohantavirus genus page).

Physicochemical and physical properties

Only known for members of the genus Orthohantavirus (see Orthohantavirus genus page).

Nucleic acid

Hantavirids have tri-segmented, negative-sense RNA genomes (S, M, and L segments). The viral mRNAs are not polyadenylated and contain a 5′-methylated cap and several non-templated nucleotides at the 5′-end that are derived from host cell mRNAs via cap snatching (Schmaljohn et al., 1985, Jonsson and Schmaljohn 2001, Vaheri et al., 2013). Further information is only known for members of the genus Orthohantavirus (see Orthohantavirus genus page).

Proteins

Hantavirids typically express three structural proteins. The most abundant structural protein in a hantavirion is N, which encapsidates the hantaviral genomic segments. The least abundant protein is L, which mediates viral genome replication and transcription. Two glycoprotein subunits, G_N and G_C, are produced from GPC and mediate entry of hantavirions (Schmaljohn et al., 1985, Spiropoulou 2001, Vaheri et al., 2013). Specifics are only known for members of the genus Orthohantavirus (see Orthohantavirus genus page).

Lipids

Not reported but are likely derived from the Golgi apparatus and/or the host cell plasma membrane and therefore likely composed of phospholipids, glycolipids, fatty acids, and sterols.

Carbohydrates

Only known for members of the genus Orthohantavirus (see Orthohantavirus genus page).

Genome organization and replication

S RNA encodes N and in some viruses NSs (Jääskeläinen et al., 2007, Vera-Otarola et al., 2012), M RNA encodes GPC, and the L RNA encodes L with its RdRP, helicase, and endonuclease domains (Jonsson and Schmaljohn 2001) (Figure 1 Hantaviridae). Specifics are only known for members of the genus Orthohantavirus (see Orthohantavirus genus page).

Figure 1 Hantaviridae. Genome organization of representative hantaviruses. The 5′- and 3′- ends of all segments are complementary at their termini, likely promoting the formation of panhandle RNP complexes within the virion. GPC, glycoprotein precursor gene; L, large (protein) gene; N, nucleoprotein gene.

Biology

Hantavirids have been found in actinopterygian (lophiid, percid, ogcocephalid, and triacanthodid, and possibly goblid and melanotaeniid) and agnathan (myxinid) fish; in emballonurid, hipposiderid, pteropodid, rhinolophid, verspertillionid, and possibly molossid and nycterid bats; in soricid and talpid eulipotyphla; in muroid and possibly dipodoid rodents; in gekkonid and possibly scincid reptiles; and potentially in coleopteran and plectopteran insects (see genus pages for details). Only orthohantaviruses are known to cause diseases (see Orthohantavirus genus page).

Antigenicity

Systematic antigenicity studies have only been reported for orthohantaviruses (see Orthohantavirus genus page).

Derivation of names

Actantavirinae: after the fish class Actinopterygii and hantavirus
Actinovirus: after the fish class Actinopterygii 
Agantavirinae: after the fish infraphylum Agnatha and hantavirus 
Agnathovirus: after the fish infraphylum Agnatha 
andesense: after the Andes mountain range, South America 
asamaense: after the Asama River, Japan 
asikkalaense: after Asikkala, Finland 
bayoui: after the Latin bayouus, meaning bayou 
bernense: after Bern, Switzerland 
boweense: after Bowé, Guinea 
brugesense: after Bruges, Belgium 
brunaense: after the Latin Bruna, meaning Brno, Czech Republic 
caobangense: after Cao Bằng Province, Vietnam 
chocloense: after the cantina (bar) “El Choclo”, Panama 
dabieshanense: after 大別山 (Dàbiéshān), China 
delgaditoense: after Caño Delgadito, Venezuela 
dobravaense: after Dobrava in Slovenia 
eptatreti: after the fish genus Eptatretus 
fugongense: after 福贡县 (Fúgòng County), China 
halieutaeae: after the fish genus Halieutaea 
hantanense: after 한탄강 (Hantan River), South Korea 
Hantaviridae: after Hantaan virus 
hemidactyli: after the reptilian genus Hemidactylus 
imjinense: after 임진강 (Imjin river), South Korea 
jejuense: after 제주도 (Jeju Island), South Korea 
kenkemeense: after Кенкеме (Kenkeme river), Russia 
khabarovskense: after Хабаровск (Khabarovsk), Russia 
laibinense: after 来宾 (Láibīn), China 
lenaense: after Ле́на (Lena river), Russia 
Loanvirus: after 龙泉 (Lóngquán), China 
longquanense: after 龙泉 (Lóngquán), China 
lophii: after the fish genus Lophius 
luxiense: after 泸溪县 (Lúxī County), China 
Mammantavirinae: after the animal class Mammalia and hantavirus 
maporalense: after Hato Maporal farm, Venezuela 
Mobatvirus: after mole and bat 
montanoense: after a geographical feature or location (Montaño) in or near Leonardo Bravo municipality, Mexico 
moroense: after El Moro Canyon, USA 
necocliense: after Necoclí Municipality, Colombia 
negraense: after Laguna Negra, Paraguay 
nigrorivense: after the Latin nigro, meaning black and the Latin rivus, meaning river 
novaense: after Nova, Hungary 
Orthohantavirus: from the Ancient Greek ὀρθός (orthós), meaning straight, right, proper and Hantaan virus 
oxbowense: after Oxbow Regional Park, USA 
prospectense: after Prospect Hill, USA 
puumalaense: after Puumala Municipality, Finland 
quezonense: after Quezon Memorial National Park, Philippines 
Repantavirinae: after the animal class Reptilia and hantavirus 
Reptillovirus: after the animal class Reptilia 
robinaense: after Robina, Australia 
rockportense: after Rockport, USA 
sangassouense: after Sangassou, Guinea 
seewisense: after Seewis im Prättigau, Switzerland 
seoulense: after Seoul, South Korea 
sinnombreense: after Sin Nombre canyon, USA 
tatenalense: after historic Tatenale, England 
thailandense: after Thailand 
thottapalayamense: after Thottapalayam, India 
Thottimvirus: after Thottopalayam virus 
tigrayense: after ትግራይ (Tigray Region), Ethiopia 
triacanthodis: after the fish genus Triacanthodes 
tulaense: after Тула (Tula), Russia 
xuansonense: after Xuân Sơn, Vietnam 
yakeshiense: after 牙克石 (Yákèshí), China

Subfamily, genus and species demarcation criteria

The availability of at least coding-complete sequences of all three genome segments may be sufficient for hantavirid classification in the absence of a cultured isolate. Demarcation of genera is based upon DivErsity pArtitioning by hieRarchical Clustering (DEmARC) analysis) using concatenated deduced S, M, and L segment expression product sequences (Hantaviridae: current classification and future perspectives, Viruses, 11, 9, e0788">Laenen et al., 2019). DEmARC analysis gave a frequency distribution of Pairwise Evolutionary Distance (PED) values of which the threshold of 0.1 gave an optimal clustering cost of zero and is used as the hantavirid species demarcation criterium. Genera are demarked by a PED-value threshold of 0.95 and subfamilies are demarcated based on their distinct clustering in a Bayesian maximum clade credibility tree and a PED-value threshold of 3.5.

Relationships within the family

Phylogenetic relationships across the family have been estimated using Bayesian maximum clade credibility trees generated from complete N, GPC, and L amino-acid sequences; similar topologies are obtained with concatenated N and GPC sequences (Figure 2 Hantaviridae).

Figure 2 Hantaviridae. Maximum likelihood phylogenetic tree inferred using IQ-TREE. The tree was constructed based on 53 concatenated S and M segment (amino acid) sequences using the LG+R9 model of sequence evolution. Branch lengths represent the estimated number of substitutions per site. Bootstrap support values (>70%) are indicated at nodes, reflecting the degree of confidence in the branching pattern.

Relationships with other taxa

Hantavirids are closely related to bunyaviral crulivirids, fimovirids, peribunyavirids, phasmavirids, tulasvirids, and tospovirids (Wolf et al., 2018, Herath et al., 2020).

Related, unclassified viruses

Virus names and virus abbreviations are not official ICTV designations.

Additional unclassified hantavirids that are probable members of established genera are listed under individual genus descriptions.