Family: Arenaviridae

Genus: Reptarenavirus

Distinguishing features

Like hartmaniviruses, but unlike antennaviruses and mammarenaviruses, reptarenaviruses infect snakes. Whereas some reptarenaviruses are known to cause boid inclusion body disease (BIBD) in snakes (Hetzel et al., 2013, Stenglein et al., 2012), hartmaniviruses have yet to be associated with any disease. Reptarenaviruses are notable for encoding a glycoprotein GP2 that is more similar in structure to those of ebolaviruses (order Mononegavirales, family Filoviridae) than to those encoded by antennaviruses, hartmaniviruses, and mammarenaviruses. In addition, the hartmanivirus and mammarenavirus stable signal peptide (SSP), which remains associated with the GP complex, is lacking in the reptarenavirus GP complex (Koellhoffer et al., 2014). 

Virion

Morphology

Virions are spherical or pleomorphic in shape, 100–200 nm in dimeter, with dense lipid envelopes (Figure 1. Reptarenavirus). The virion surface layer is covered with club-shaped projections. These projections are 10 nm long, made of trimeric spike structures of two virus-encoded membrane GP subunits (GP1 and GP2), and are spaced 11–15 nm apart. Like the virions of mammarenaviruses, but unlike those of antennaviruses and hartmaniviruses, the virions of reptarenaviruses contain a Z layer under the membrane. In contrast to mammarenaviruses, no second layer exists beneath the membrane (Hetzel et al., 2013). 

Figure 1. Reptarenavirus.  A) Cryo-electron micrograph of University of Helsinki virus 1 (UHV-1). Courtesy of Pasi Laurinmäki and Sarah Butcher, Cryo-EM Core Facility, Biocenter Finland, University of Helsinki, Finland. B) Negative-stain electron micrograph of UHV-1. Courtesy of Inki Luoto, University of Helsinki, Finland.

Physicochemical and physical properties

Not reported.  

Nucleic acid

Virions contain 2 ambisense single-stranded RNA segments that are encapsidated independently. The termini of the RNAs contain inverted complementary sequences encoding transcription and replication initiation signals (Hetzel et al., 2013, Hepojoki et al., 2018, Stenglein et al., 2012). 

Proteins

Viruses express 4 structural proteins. The most abundant structural protein in an arenavirion is nucleoprotein (NP), which encapsidates the virus genomic segments. The least abundant protein is the RNA-directed RNA polymerase (L), which mediates virus genome replication and transcription. The zinc-binding matrix protein (Z) functions as a matrix protein. Unlike mammarenavirus Z, reptarenavirus Z does not possess an N-terminal glycine residue typically associated with myristoylation for membrane anchoring. Instead, reptarenavirus Z has a predicted transmembrane domain located in the first 50 amino acid residues that may serve a similar role. Reptarenavirus Z also does not contain late budding motifs. Instead, these motifs are found at the C-termini of the NP protein. Glycoproteins (GP1 and GP2) are derived by post-translational cleavage from an intracellular glycoprotein precursor, GPC. Reptarenaviruses do not produce SSP, as do hartmaniviruses and mammarenaviruses, and the reptarenavirus GP complex is unique to the genus (Hetzel et al., 2013, Koellhoffer et al., 2014, Stenglein et al., 2012). 

Lipids

Not reported. 

Carbohydrates

Not reported. 

Genome organization and replication 

The small (S) and large (L) RNAs of reptarenaviruses encode two proteins in non-overlapping open reading frames (ORF) of opposite polarities (ambisense coding arrangement) that are separated by non-coding intergenic regions (IGRs) (Figure 2. Reptarenavirus). The S RNA encodes NP in the virus genome-complementary sequence, and virus glycoprotein precursor (GPC) in the virus genome-sense sequence. The L RNA encodes L in the virus genome-complementary sequence, and Z in the virus genome-sense sequence. The IGRs form one or more energetically stable stem-loop (hairpin) structures and function in structure-dependent transcription termination and in virion assembly and budding (Hetzel et al., 2013, Stenglein et al., 2012). In contrast to mammarenaviruses and hartmaniviruses, there is evidence that virus recombination events occur in snakes infected with reptarenaviruses (Stenglein et al., 2015). 

Figure 2. Reptarenavirus.  Schematic representation of the bisegmented reptarenavirus genome organization. The 5'-and 3'-ends of both segments (S and L) are complementary at their termini, likely promoting the formation of circular ribonucleoprotein complexes within the virion. GPC, glycoprotein precursor; L, RNA-directed RNA polymerase; NP, nucleoprotein; Z, zinc-binding matrix protein. Intergenic regions (IGRs), which form hairpin structures (not shown), separate open reading frames.

Biology

Some reptarenaviruses can cause boid inclusion body disease (BIBD) in snakes (Hetzel et al., 2013, Stenglein et al., 2012). BIBD is an infectious disease that can be acute or chronic in snakes belonging to the families Boidae and Pythonidae. In boas (Squamata: Boidae: Boa Linnaeus, 1758), the disease outcome varies; affected animals either die within weeks or months or become asymptomatic (chronic) reptarenavirus carriers. In contrast, pythons generally develop severe fatal neurological symptoms within a few weeks. Virus replication sites also differ between snakes of both families. High virus loads of reptarenaviruses may be detected in multiple tissues or excreta of boas (blood, liver, lung, tonsil, spleen, kidney, colon, trachea, brain, feces, urates, skin shed), whereas virus replication is limited to the CNS tissues in pythons (Stenglein et al., 2017). Virus immunosuppression is thought to be a significant component of the disease. However, snakes do develop antibodies against reptarenaviruses (Hetzel et al., 2013, Korzyukov et al., 2016, Windbichler et al., 2019). In some cases, animals may possibly clear reptarenavirus infections without developing BIBD. 

It remains unclear whether snakes are the natural host of reptarenaviruses or if snakes are infected incidentally. Thus far, reptarenaviruses have only been found in captive snakes. Likewise, although horizontal and vertical transmission of reptarenaviruses has been reported in boa constrictors, the mechanism of transmission of these viruses remains unclear. Several studies have identified multiple reptarenaviruses in the same snake, indicating that coinfections are common (Hepojoki et al., 2015, Stenglein et al., 2015, Keller et al., 2017). 

In experimental settings, reptarenaviruses can infect laboratory mice, causing mild to moderate lesions (without fatality) in the liver, kidney, spleen, brain and lungs (Abba et al., 2017). 

Antigenicity

Antibodies against the mammarenaviruses lymphocytic choriomeningitis virus (LCMV) NP and Machupo virus (MACV) NP react weakly with the NP of the reptarenavirus University of Helsinki virus 1 (UHV-1). Human and rabbit anti-MACV sera also recognize UHV-1 NP (Hetzel et al., 2013). Systematic antigenicity studies for reptarenavirions have yet to be reported. 

Derivation of names

Reptarenavirus: from the Latin repere meaning “creep” or “crawl”, a reference to the reptilian hosts of reptarenaviruses (Radoshitzky et al., 2015). 

Species demarcation criteria

The parameters used to assign viruses to different species in the genus are:

• virus shares less than 80% nucleotide sequence identity in the S segment and less than 76% identity in the L segment;
• association of the virus with a distinct main host or a group of sympatric hosts;
• dispersion of the virus in a distinct defined geographical area;
• association (or not) with human disease;
• virus shares less than 88% NP amino acid sequence identity (Radoshitzky et al., 2015). 

Relationships within the genus

Phylogenetic relationships across the genus have been established from maximum likelihood trees generated from full or partial sequences of NP and L proteins (Figure 3. Reptarenavirus).  

Member species

The Member Species table enumerating important virus exemplars classified under each species of the genus is provided at the bottom of the page.

Related, unclassified viruses 

Virus names and virus abbreviations are not official ICTV designations. 

* Coding region sequence incomplete.