Hytrosaviridae - v201911


Hytrosaviridae - v201911

Henry M. Kariithi, Just M. Vlak, Johannes A. Jehle, Max Bergoin, Drion G. Boucias and Adly M. M. Abd-Alla

Chapter contents

Posted June 2019

Hytrosaviridae: The family

Member taxa

Supporting information

  • Authors - corresponding authors: Adly M. M. Abd-Alla (a.m.m.abd-Alla@iaea.org)
  • Resourcessequence alignments and tree files
  • References

Citation

A summary of this ICTV Report chapter has been published as an ICTV Virus Taxonomy Profile article in the Journal of General Virology, and should be cited when referencing this online chapter as follows:

Henry M. Kariithi, Just M. Vlak, Johannes A. Jehle, Max Bergoin, Drion G. Boucias, Adly M. M. Abd-Alla, and ICTV Report Consortium, 2019, ICTV Virus Taxonomy Profile: Hytrosaviridae, Journal of General Virology, 100, 1271–1272.

Summary

Hytrosaviruses (also known as salivary gland hypertrophy viruses, SGHVs) are large, rod-shaped, enveloped, pathogenic viruses of dipterans with circular dsDNA genomes of 124–190 kbp. Hytrosaviruses infect the hematophagous tsetse flies and the filth-feeding houseflies and are classified into two genera, Glossinavirus (with the single species Glossina hytrovirus) and Muscavirus (with the single species Musca hytrovirus) respectively. Note that the spelling of “hytrovirus” in these species names differs from that of the family name; a future Taxonomic Proposal will seek to remedy this nomenclatural discrepancy. Members of both genera, Glossina pallidipes salivary gland hypertrophy virus (infecting the tsetse fly) and Musca domestica salivary gland hypertrophy virus (infecting the housefly), have been fully sequenced. Members of the two genera have distinct genome sizes, host ranges and transmission modes. Hytrosaviruses primarily replicate in the salivary glands (SGs) of adult flies, thereby inducing SG hypertrophy syndrome (SGH). SGHVs, also replicate in other host tissues (e.g. trachea, milk glands, corpora allata/cardiaca) in which they do not induce hypertrophy. Muscavirus infections are strictly overt, while glossinavirus infections can be covert or overt. SGH-positive flies are almost always infertile. PCR-based estimates of the prevalence of hytrosaviruses in the field range from 1–88%. An unclassified hytrosavirus has been reported in the phytophagous narcissus bulb fly Merodon equestris.

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

Characteristic

Description

Typical member

Glossina pallidipes salivary gland hypertrophy virus (EF568108), species Glossina hytrovirus#, genus Glossinavirus

Virion

Typically, enveloped particles of 50–80 × 500–1000 nm

Genome

Circular, dsDNA, 124–190 kbp, encoding 108–174 proteins

Replication

DNA synthesis and transcription within nuclear replication complexes; temporal expression of genes; nucleocapsids exit the nucleus via nuclear pore complex, then associate with the Golgi apparatus resulting in cytoplasmic envelopment and virion assembly

Translation

Presumably via cap-dependent, polyadenylated monocistronic mRNAs

Pathogenicity

Infection induces salivary gland hypertrophy (SGH) syndrome, reproductive dysfunctions and sterility in flies

Host range

Dipterans: tsetse flies spp. (Glossinavirus); housefly and stable fly (Muscavirus)

Taxonomy

Two genera (Glossinavirus and Muscavirus) each including a single species

# Note that the spelling of “hytrovirus” in this species names differs from that of the family name; a future Taxonomic Proposal will seek to remedy this inconsistency.

Virion

Morphology

Virions are 50–80 nm in diameter, non-occluded, non-icosahedral rod-shaped particles (500–1000 nm in length) and contain a bilayer lipid envelope (Abd-Alla et al., 2009, Garcia-Maruniak et al., 2009, Kariithi et al., 2013b, Orlov et al., 2018) (Figure 1A.Hytrosaviridae and 1D.Hytrosaviridae). Particles are bipolar with rounded and/or conical ends (Kariithi et al., 2013b, Orlov et al., 2018, Garcia-Maruniak et al., 2008) (Figure 1B.Hytrosaviridae and 1C. .Hytrosaviridae). The dense internal capsid shows a helical organization and the envelope contains virus-encoded proteins with protruding, regularly-spaced and helically oriented glycoprotein spikes, presumably composed of protein dimers or braided, bead-like structures (Kariithi et al., 2013b, Orlov et al., 2018, Kariithi et al., 2010). Descriptions of members of the two individual hytrosavirus genera are detailed in the corresponding sections.

Figure 1.Hytrosaviridae. Micrographs showing the structural features of Glossina pallidipes salivary gland hypertrophy virus – Uganda. (A) Transmission electron micrographs showing the main structural features of a virus particle. Inset in Panel A shows a cross-section indicating the nucleocapsid core, tegument, envelope and coating layer; (B) Negative-staining of a virion showing the helical organization of the coating protein. (C and D) Cryo-EM tomograms of the central section of virions exhibiting the same polarity with round (left [) and conical (right >) extremities. The four core parts of the virion including the spikes forming the coating layer, the envelope, the tegument and the nucleocapsid are labelled in light purple, green, turquoise and salmon, respectively. All scale bars in panels B–D are 100 nm. Micrographs in Panels A and B–D were adapted from (Kariithi et al., 2017a) and (Orlov et al., 2018), respectively.

Physicochemical and physical properties

Virus particles have a density of 1.153 g cm-3 in Nycodenz gradients.

Nucleic acid

The hytrosavirus genome is a single copy of circular dsDNA of approximately 124 kbp (Muscavirus) or 190 kbp (Glossinavirus) (Garcia-Maruniak et al., 2009, Garcia-Maruniak et al., 2008, Abd-Alla et al., 2008, Abd-Alla et al., 2016). The majority of the hytrosavirus genes have 5′-terminal TATA-box promoter sequences, immediate early promoters with the CAGT promoter motif, the canonical baculovirus late (T/G/A)TAAG transcriptional initiation motifs and a 3′-terminal polyadenylation signal (Garcia-Maruniak et al., 2009, Abd-Alla et al., 2016).

Proteins

Hytrosavirus genomes contain 108 (Muscavirus) or 160–174 (Glossinavirus) putative genes (Garcia-Maruniak et al., 2008, Abd-Alla et al., 2008, Abd-Alla et al., 2016). Members of the genera Muscavirus and Glossinavirus encode at least 29 and 57 proteins, respectively, which are associated with the nucleocapsid, tegument and the envelope fractions of virus particles (Kariithi et al., 2013b, Garcia-Maruniak et al., 2008, Abd-Alla et al., 2016). Glossinavirus virions also contain 51 host-derived (cellular) proteins, 38 of which are associated with the viral tegument and the remaining 13 are potentially incorporated into virions (Kariithi et al., 2013b).

Lipids

Hytrosaviruses acquire their lipid envelopes through cytoplasmic assembly by budding through endoplasmic/Golgi membranes (Kariithi et al., 2013b, Orlov et al., 2018, Boucias et al., 2013a, Lietze et al., 2011c).

Carbohydrates

Unknown.

Genome organization and replication

All hytrosaviruses have a similar organization of their circular dsDNA genome. The genome of members of the genus Glossinavirus (190 kbp) is about 65 kbp longer than that of members of the genus Muscavirus (124 kbp), contains 52–66 more putative non-overlapping genes and has a significantly lower G+C content (28% vs. 44%) (Garcia-Maruniak et al., 2009, Garcia-Maruniak et al., 2008, Abd-Alla et al., 2008, Abd-Alla et al., 2016). The conserved regions in the genome of the two known glossinavirus strains are 98.1% identical at the nucleotide level, compared to a lower collinearity (25–73%) between the corresponding regions in the muscavirus genome (Figure 2.Hytrosaviridae) (Abd-Alla et al., 2009, Garcia-Maruniak et al., 2009, Abd-Alla et al., 2016). Genes are distributed equally over both DNA strands and occur in unidirectional clusters (Figure 3.Hytrosaviridae). Approximately 2.8% and 1.7% of the glossinavirus and muscavirus genomes, respectively, contain homologous repeat sequences (hrs). The glossinavirus genome contains a total of 14 direct repeats sequence (drs; composed of 51–246 bp units) compared to 18 drs in the muscavirus genome (composed of 9–149 bp units). In addition, one inverted repeat sequence occurs in the glossinavirus genome (but not in the muscavirus genome). The drs are clustered in certain regions on the genomes, but they are less clustered in muscaviruses than in glossinaviruses (Garcia-Maruniak et al., 2009, Garcia-Maruniak et al., 2008, Abd-Alla et al., 2008, Abd-Alla et al., 2016). In contrast to other large invertebrate dsDNA viruses, approximately 50% of the drs are localized within specific ORFs and are thought to be origins of viral DNA replication and/or act as transcriptional enhancers.

Figure 2.Hytrosaviridae. Collinearity of the conserved regions of Ugandan and Ethiopian glossinavirus isolates (GpSGHV-Eth and GpSGHV-Uga, A) compared with muscavirus (B): The red lines in A and B) indicate identity levels of regions (not ORF) between the viruses, whilst the blue lines (in B) indicate inversions. The white bands represented in the thick black lines do not necessarily indicate the open reading frames (ORFs), but rather the conserved genomic regions. The figure was adapted from (Abd-Alla et al., 2016). 

Figure 3.Hytrosaviridae. Circular representation of the genome of Glossina pallidipes salivary gland hypertrophy virus (Ethiopia strain): Putative open reading frames are indicated by boxes on the blue (clockwise transcription) or yellow (anti-clockwise transcription) circles, with those encoding virion proteins indicated by salmon colour. Alphabetical numbers on the innermost ring represent BglII restriction fragments, while green boxes on the genome circle indicate the position of the direct repeat sequences. Information derived from (Abd-Alla et al., 2016).

Hytrosaviruses primarily replicate in viral replication complexes in the nuclei of the host’s SGs cells, but also in non-SG tissues (e.g. milk glands, corpora allata/cardiaca) (Garcia-Maruniak et al., 2009, Kariithi et al., 2017b). Orally ingested hytrosaviruses exploit the tracheal system as a conduit to breach basal laminal barrier in the midgut to access other tissues including the SGs (Lietze et al., 2011c). Infection is thought to initiate via attachment to unknown host receptors followed by internalization (Kariithi et al., 2011). The fusion of viral and host vesicle membranes eventually results in the release of the capsids into the cytoplasm, which are then trafficked to the cell nucleus where the genome is released for gene transcription and genome replication, packaging and assembly of progeny nucleocapsids in the virogenic stroma (Kariithi et al., 2013b, Lietze et al., 2011c, Kariithi et al., 2011). Hytrosavirus replication is thought to involve the sequential expression of immediate early (transcription factors), early (DNA replication genes), and late (viral replication proteins) genes (Kariithi et al., 2013b). Nucleocapsids exit the nucleus via the nuclear pore complex. Virion assembly, including the acquisition of the glycoprotein-containing envelopes, occurs in the cytoplasm. Mature particles egress by budding through (Muscavirus) or lysis of the luminal membranes of infected cells (Glossinavirus) (Kariithi et al., 2013b, Boucias et al., 2013a, Lietze et al., 2011c), into the lumen of the salivary gland. 

Antigenicity

Various proteins including the major envelope protein p74 of glossinaviruses have been identified as immunogenic in rabbit (Kariithi et al., 2010).

Biology

Known hytrosaviruses are restricted to three dipteran insects; the hematophagous tsetse flies (Glossina spp.), the filth-feeding housefly, Musca domestica, and the phytophagous syrphid fly Merodon equestris (Abd-Alla et al., 2009). The distinct biological characteristics of members of the genera Glossinavirus and Muscavirus are described in the corresponding genus pages.

Pathogenicity

The salient diagnostic feature of hytrosavirus infection is the induction of salivary gland hypertrophy (SGH) syndrome in the SGs of infected flies (Figure 4A.Hytrosaviridae and 4C.Hytrosaviridae) (Abd-Alla et al., 2009). Muscavirus-infected SGs are hypertrophic (i.e. contain uniformly infected cells with enlarged cytoplasmic and nuclear compartments) (Figure 4B.Hytrosaviridae), while glossinavirus-infected SGs are hyperplastic (i.e. contain multi-layered dividing cells) (Figure 4D.Hytrosaviridae). Hytrosavirus infection causes reproduction dysfunctions and sterility (Kariithi et al., 2017b, Abd-Alla et al., 2010). The pathogenetic characteristics that distinguish members of the two Hytrosaviridae genera are described in the corresponding genus pages.

Figure 4.Hytrosaviridae. Micrographs showing the pathogenicity of salivary gland hypertrophy viruses: (A) Light micrographs of hypertrophied salivary glands (SGs) dissected from Musca domestica infected by muscavirus. (B) Muscavirus-induced cellular hypertrophy in housefly SGs. (C) Hyperplastic SGs of tsetse. (D) Glossinavirus-induced hyperplasia in tsetse SGs. Figure source: (Kariithi et al., 2017a).

Derivation of names

Hytrosaviridae: from the Greek Hypertrophia meaning excess nourishment and sialoadenitis meaning salivary gland inflammation (Abd-Alla et al., 2009).

Phylogenetic relationships

Phylogenetically, the 190 kbp genome of glossinavirus has limited, but significant gene homology to the muscavirus 124 kb genome (Garcia-Maruniak et al., 2008, Abd-Alla et al., 2008, Abd-Alla et al., 2016), hence the placement of the hytrosaviruses into two separate genera within the family Hytrosaviridae. Based on their virus particle dimensions, members of the genus Muscavirus are more similar than those of the genus Glossinavirus to an unclassified virus that has been reported to infect the narcissus bulb fly Merodon equestris. This virus is a putative member of the Hytrosaviridae on the basis of similarity of virus particles and SGH symptomatology (Amargier et al., 1979).

Similarity with other taxa

Hytrosaviruses are structurally similar to baculoviruses, nudiviruses and nimaviruses, but differ functionally in the absence of occlusion bodies, their host ranges and predominant modes of transmission, as well as lower lethality (i.e. hytrosaviruses rarely kill their insect host) (Kariithi et al., 2018). Based on phylogenetic analysis of the DNA polymerase (dnapol) gene, which is present in all large dsDNA viruses, hytrosaviruses genomes cluster more closely with linear dsDNA genomes than with the large circular invertebrate dsDNA viruses (Figure 5.Hytrosaviridae) (Garcia-Maruniak et al., 2008, Abd-Alla et al., 2008). Among the structural and genomic features shared by hytrosaviruses and some other large dsDNA viruses are the possession of enveloped, rod-shaped virions, circular dsDNA genome, the presence of multiple interspersed direct homologous repeats and replication in the nucleus. Members of the Hytrosaviridae share 12 of the 38 core genes that have been described in baculoviruses (Javed et al., 2017, Wennmann et al., 2018). The most significant similarity between hytrosaviruses and other large invertebrate dsDNA viruses is the presence of the per os infectivity factor genes (p74/pif-0, pif-1, pif-2 and pif-3) in members of both Muscavirus and Glossinavirus (Figure 6.Hytrosaviridae). These genes are conserved in baculoviruses, nudiviruses, nimaviruses and some bracoviruses (Jehle et al., 2013), and suggest a common mechanism of host entry. Hytrosaviruses possess genes encoding several subunits of the viral DNA-directed RNA polymerase (DdRP) complex, including four late expression factor genes (lef-4, lef-5, lef-8 and lef-9) found in baculoviruses and nudiviruses (Abd-Alla et al., 2016, Jehle et al., 2013). However, lef-3 was not found in hytrosaviruses.

Figure 5.Hytrosaviridae. Phylogenetic tree of hytrosaviruses based on predicted DNA polymerase amino acid sequences. The phylogenetic tree of DNA polymerase and its homologs is based on 603 conserved aa sites in 30 viruses from various families. The evolutionary history was inferred by using the maximum likelihood method based on the JTT matrix in MEGA7 (Kumar et al., 2016). A discrete Gamma distribution was used to model evolutionary rate differences among sites (2 categories (+G, parameter = 1.5222)). All positions containing gaps and missing data were eliminated. Numbers on the nodes indicate bootstrap values (500 replicates).


Figure 6.Hytrosaviridae. Phylogenetic tree of concatenated predicted amino acid sequences of per os infectivity factor proteins (P74, PIF-1, PIF-2, PIF-3 and ODV-E66) of hytrosaviruses and their homologues in baculoviruses and nudiviruses. The evolutionary history was inferred by using the maximum likelihood method based on the JTT matrix model in MEGA7 (Kumar et al., 2016). A discrete Gamma distribution was used to model evolutionary rate differences among sites with categories and a G parameter of 1.7509 (A: Top) or 0.9778 (B: Bottom). All positions containing gaps and missing data were eliminated. Numbers on the nodes indicate bootstrap values (500 replicates). The figure was adapted from (Garcia-Maruniak et al., 2009).

 


Genus: Glossinavirus

Distinguishing features

Members of the genus Glossinavirus can switch from an asymptomatic infection to the occasional state of symptomatic infection which elicits salivary gland hypertrophy syndrome (SGH) epizootics that reduce fly fecundity and cause colony collapse (Abd-Alla et al., 2011). Intra-hemocoelic injections of glossinavirus into larvae or adults does not induce overt SGH in the same fly generation, rather, the symptoms occur in the F1 progeny (Boucias et al., 2013b, Demirbas-Uzel et al., 2018). Transmission of glossinavirus occurs both horizontally (fly-to-fly via SG secretions) and vertically (mother-to-offspring either transovarial or via milk gland secretions) (Abd-Alla et al., 2010, Boucias et al., 2013b). Viremic flies are partially sterile due to gonadal lesions and ovarian abnormalities caused by the virus (Abd-Alla et al., 2011).

Virion

Morphology

Virions are long, rigid, rod-shaped particles (approximately 50–65 nm in width and 1000 nm in length) and consist of an electron-dense helical nucleocapsid core (40 nm in diameter) surrounded by a proteinaceous tegument matrix (10 nm thick) encapsulated by an outer lipid bilayer envelope presumably containing viral glycoproteins (Figure 1A.Hytrosaviridae) (Kariithi et al., 2013b, Orlov et al., 2018). The asymmetric virions have one rounded end and one conical (Orlov et al., 2018) (Figure 1C.Hytrosaviridae and 1D.Hytrosaviridae). The outer surface of the virion is studded with left-handed helical polymeric spikes (13 nm long; 15 nm periodicity) composed of virus and host-derived protein dimers (23 spikes × 24 helical turns = 1104 envelope dimers) (Kariithi et al., 2013b, Orlov et al., 2018).

Physicochemical and physical properties

Particles have a density of 1.153 g cm-3 in Nycodenz (Kariithi et al., 2010). Virions are fragile and the envelope can be detached by treatment with common buffers (Kariithi et al., 2013b, Orlov et al., 2018, Kariithi et al., 2010).

Nucleic acid

The glossinavirus genome is a circular dsDNA molecule (Abd-Alla et al., 2008, Abd-Alla et al., 2016) that encodes homologues of 12 of the 38 so-called core genes of baculoviruses and nudiviruses that are involved in: (i) DNA replication/replication (e.g. DNA polymerase, helicases); (ii) transcription (e.g. late effector factors; LEFs); (iii) packaging, assembly and release; (iv) cell cycle arrest and /or interactions with host proteins (e.g. desmoplakin and Ac81); and (v) oral infectivity (e.g. per os infectivity factors; PIFs) (Kariithi et al., 2013b, Abd-Alla et al., 2016).

Proteins

Transcriptome and proteomic analyses provide evidence that 61 of the glossinavirus ORFs are translated into virus proteins (Kariithi et al., 2013b, Kariithi et al., 2010, Abd-Alla et al., 2016). At least 45 of these proteins are virion structural proteins, of which 10, 15 and 20 are associated with the envelope, nucleocapsid and in the tegument components of the virions, respectively (Kariithi et al., 2013b). Additionally, the virion proteome also contains 51 host-derived proteins, some of which are incorporated into the tegument matrix, where they may play specific or auxiliary roles in the virus replication cycle (Kariithi et al., 2013b).

Lipids

The virion envelope that encapsulates the tegument is composed of a lipid bilayer (Kariithi et al., 2013b, Orlov et al., 2018) but its composition is unknown.

Carbohydrates

The virion envelope and tegument potentially contain virus proteins that include NXT motifs, as well as host-derived glycoproteins acquired from the host during the cytoplasmic envelopment process of the virus (Kariithi et al., 2013b, Orlov et al., 2018).

Genome organization and replication

The genomes of the Ugandan and Ethiopian glossinavirus strains have 190,032 and 190,291 bp (28% and 27.9% G+C content) respectively, encoding 160 and 174 putative non-overlapping genes that are evenly distributed over both DNA strands in unidirectional clusters (Abd-Alla et al., 2008, Abd-Alla et al., 2016). Of the glossinavirus ORFs, ~ 90%, 84% and 36% contain TATA-like box elements, polyadenylation signals and canonical baculovirus late (T/G/A)TAAG transcriptional initiation motifs, respectively (Abd-Alla et al., 2016). Approximately 3% of the glossinavirus genome is composed of head-to-tail tandem repeat sequences, which are thought to serve as regulators of gene expression and/or origins of DNA replication (Abd-Alla et al., 2008, Abd-Alla et al., 2016). Fifty-seven genes encode structural virion proteins, while 12 genes encode non-structural proteins (Kariithi et al., 2013b, Abd-Alla et al., 2016). Glossinavirus capsids assemble in the nucleus of infected cells and are thought to acquire bilayer lipidic envelope after moving through the nuclear pores and budding through the endoplasmic/Golgi membranes (Kariithi et al., 2013b).

Antigenicity

Unknown.

Biology

Members of the genus Glossinavirus are currently restricted to the hematophagous tsetse flies (Glossina species). Virus infection reduces fecundity, sometimes resulting in the collapse of laboratory colonies of some tsetse species such as Glossina pallidipes (Abd-Alla et al., 2010). Tsetse flies are not highly susceptible to glossinavirus infection; injection of millions of glossinavirus virions results in only a small fraction of the injected flies developing SGH (Boucias et al., 2013b, Demirbas-Uzel et al., 2018). There is no available cell culture systems capable of supporting glossinavirus replication (Arif and Pavlik 2013).

Host range

Tsetse flies are the natural (currently the only known) hosts for members of the genus Glossinavirus; infections can either be chronically asymptomatic or cause severe and acute symptomatic SGH syndrome (Abd-Alla et al., 2010). Members of the genus Glossinavirus are highly specific to Glossina species and are not known to induce overt SGH in heterologous hosts such as housefly (Abd-Alla et al., 2011, Boucias et al., 2013b). The susceptibility of tsetse flies to glossinavirus infections varies widely amongst different Glossina species; G. pallidipes is the most susceptible (Demirbas-Uzel et al., 2018). There is genetic spatial variation among glossinavirus isolates from different Glossina species (Kariithi et al., 2013a, Meki et al., 2018).

Transmission

Virus transmission is both horizontal (fly-to-fly) via salivary gland secretions and vertical (mother-offspring) via milk gland secretions and trans-ovarially (Abd-Alla et al., 2010, Abd-Alla et al., 2011, Boucias et al., 2013b). There is no evidence for mechanical transmission of glossinavirus. The solitary nature of the tsetse fly host is compatible with vertical transmission of glossinavirus in the field.

Geographical distribution

The specificity of glossinavirus to Glossina species restricts the geographical distribution of the virus in regions where tsetse flies occur, i.e. sub-Saharan Africa countries (Kariithi et al., 2013a, Meki et al., 2018).

Pathogenicity

Glossinavirus-induced SGH (Figure 4C.Hytrosaviridae) is associated with testicular degeneration, ovarian abnormalities, compromised development, survival, fertility and fecundity of infected tsetse flies (Abd-Alla et al., 2010). Virus infection affects sperm production and avidity of tsetse males and causes partial sterility in females (Mutika et al., 2012). Overt SGH symptoms are more prevalent in G. pallidipes, and even in this species, overt SGH symptoms are an exception rather than the rule; the factors that trigger the switch from asymptomatic to symptomatic infection states are unknown (Abd-Alla et al., 2010, Abd-Alla et al., 2011, Demirbas-Uzel et al., 2018, Kariithi et al., 2013a, Abd-Alla et al., 2013). Glossinavirus-infected SGs contain layers of dividing cells, which result in hyperplasia; in part due to cell proliferation responses resulting from virus reprogramming of the differentiated gland cells (Figure 4D.Hytrosaviridae) (Kariithi et al., 2013b, Kariithi et al., 2017a). Virus replication in other cells such as the tracheal cells and milk glands can also result in extensive hypertrophy, but without hyperplasia. Artificial injection of virus suspensions into adult flies does not result in overt SGH symptoms in the same (parental) generation, but rather in the F1 progeny, implying that the injected virus is unable to reach and replicate in fully differentiated SGs of adult flies (Boucias et al., 2013b, Demirbas-Uzel et al., 2018).

Species demarcation criteria

No demarcation criteria are defined yet since there is only a single species (Glossina hytrovirus) in this genus. Two lineages of the species can be demarcated based on differences in gene contents (nucleotide and deduced amino acid data), pathogenicity in different G. pallidipes sub-populations (Abd-Alla et al., 2016), and possibly host eco-geography (Kariithi et al., 2013a, Meki et al., 2018).

Member species

Species Virus name(s) Exemplar isolate Exemplar accession number Exemplar RefSeq number Available sequence Other isolates Other isolate accession numbers Virus abbreviation Isolate abbreviation
Glossina hytrovirus Glossina pallidipes salivary gland hypertrophy virus Uganda EF568108 NC_010356 Complete genome GpSGHV
Glossina hytrovirus Glossina pallidipes salivary gland hypertrophy virus Ethiopian KU050077 GpSGHV
Virus names, the choice of exemplar isolates, and virus abbreviations, are not official ICTV designations.

Genus: Muscavirus

Distinguishing features

Nucleocapsids of muscaviruses have regularly spaced braided, bead-like surface projections and virion particles that are more stable than those of glossinaviruses (Kariithi et al., 2010, Kariithi et al., 2017a). Members of the genus Muscavirus infect and cause only symptomatic salivary gland hypertrophy syndrome (SGH) in houseflies; the virus induces rapid cellular and nuclear hypertrophy in the SGs within 2–3 days post-infection (Lietze et al., 2012). Topical exposure or injection of members of the genus Muscavirus into adult houseflies results in overt SGH and total shutdown of oogenesis. There is no evidence for vertical transmission of this virus (Kariithi et al., 2017b, Lietze et al., 2007). Members of the genus Muscavirus are globally distributed within populations of the synanthropic housefly (Prompiboon et al., 2010), and can infect other muscids (Geden et al., 2011a). The virus induces total shutdown of vitellogenesis and sterility in viremic females, which refuse to copulate when paired with healthy males (Kariithi et al., 2017b).

Virion

Morphology

The elongated, enveloped rod-shaped muscavirus virion measures 65×550 nm, contains a unique braided, bead-like surface topography, and has rounded ends (Garcia-Maruniak et al., 2008).

Physicochemical and physical properties

Muscavirus particles sediment at a density of 1.153 g cm-3 when subjected to 10–60% Nycodenz gradient centrifugation (Coler et al., 1993), and are more stable, potentially accounting for the higher infectivity of muscaviruses compared to glossinaviruses (Kariithi et al., 2017a).

Nucleic acid

The muscavirus genome is a circular dsDNA molecule of 124,279 bp encoding 108 non-overlapping ORFs that are evenly distributed over the two DNA strands and arranged in unidirectional clusters; 101 ORFs have been validated to be transcriptionally active (Garcia-Maruniak et al., 2009, Garcia-Maruniak et al., 2008, Salem et al., 2009). Several pairs of transcripts distributed across the muscavirus genome overlap (in unidirectional, convergent, or divergent pattern), some of which are transcribed in tandem. The 3′-ends of 95 of the 108 ORFs contain polyadenylation signals (Salem et al., 2009). Similar to other circular dsDNA viruses of invertebrates, the muscavirus genome contains multiple regions with tandem repeats.

Proteins

Of the 108 ORFs in the muscavirus genome, 29 encode structural proteins (Garcia-Maruniak et al., 2008). Amongst the key viral proteins are proteins involved in the replication of the virus genome (i.e. DNA polymerase and helicase) and six homologs to the baculovirus core conserved proteins involved in per os infection (P74, PIF-1, PIF-2, PIF-3, ODV-e66 and Ac150) (Garcia-Maruniak et al., 2008). Also notable of the muscavirus proteins are those which display homology to proteins involved in the disruption of peritrophic matrix (zinc-dependent matrix metalloproteinase), in nucleotide transport/metabolism (dUTP pyrophosphatase), inhibition of apoptosis, synthesis of DNA precursors and replication and cell division (thymidylate synthase and dihydrofolate reductase), or are homologs of several cellular proteins (Garcia-Maruniak et al., 2008).

Lipids

Unknown.

Carbohydrates

Unknown.

Genome organization and replication

The circular dsDNA genome of muscavirus is 124,279 bp with a G+C content of 43.5% and encodes 108 putative methionine-initiated ORFs. Only 30 of these ORFs encode proteins homologous to known proteins (Garcia-Maruniak et al., 2008). These homologs include several proteins reported in baculoviruses and nudiviruses (P74, PIF-1, -2, -3, ODV-E66, RR1, RR2, IAP, dUTPase, MP, Ac81-like, and LEFs 4, 5, 8, 9), seven proteins described in nudiviruses (MCP, DHFR, TS, TK, and three unknown proteins), and several cellular proteins (Garcia-Maruniak et al., 2008). The muscavirus genome contains 18 direct repeats covering approximately 1.7% of the genome; seven of these repeats are located inside putative coding sequences (Garcia-Maruniak et al., 2009).

Replication of viral DNA and production of nucleocapsids occurs in the virogenic stroma of the infected SG nuclei, after which they migrate and align to the nuclear membranes and exit the nucleus via the nuclear pore complex into the cytoplasm (Boucias et al., 2013a). The nucleocapsids acquire their envelope within the cytoplasm in areas adjacent to the nuclear membranes and from peptides associated with the ribosomes (Boucias et al., 2013a, Lietze et al., 2011a). The mature virions migrate to and bud out of the plasmalemma bordering the salivary gland lumens (Lietze et al., 2011a).

Antigenicity

A major envelope protein (MdHV96) of muscaviruses has been identified as immunogenic in mice/rabbit (Boucias et al., 2013a).

Biology

Members of the genus Muscavirus specifically induce symptomatic infections (SGH) in the common housefly, which is highly susceptible to the virus; injection of ~100 viral particles results in SGH in all injected flies (Lietze et al., 2007). This virus can infect other muscids, including the stable fly Stomoxys calcitrans (Geden et al., 2011a), but without induction of overt SGH symptoms. Different geographical muscavirus strains have similar molecular and biological properties, with the prevalence of virus-infected flies varying spatially and temporally (0–40%) amongst housefly populations (Prompiboon et al., 2010). There is no available cell culture system capable of supporting muscavirus replication (Arif and Pavlik 2013).

Host range

The common housefly (Musca domestica) is the natural host for members of this genus, in which infection is symptomatic (overt SGH) (Lietze et al., 2012, Lietze et al., 2011b). Under experimental conditions, members of the genus Muscavirus can infect other muscids (e.g. lesser housefly, face fly, stable fly and tsetse fly), but without induction of diagnostic SGH (Geden et al., 2011b). However, muscavirus-challenged stable flies (Stomoxys calcitrans) and black dump flies (Hydrotaea aenescens) produce significantly fewer eggs (Geden et al., 2011a, Geden et al., 2011b).

Transmission

The transmission of muscaviruses is primarily horizontal, either orally among adult flies co-feeding on virus-contaminated food substrates, or via holding flies in virus-contaminated fly cages (Geden et al., 2008, Lietze et al., 2009). Mechanical transmission (trans-cuticular via wounds) has been suggested (Vallejo et al., 2013). There is no evidence of vertical (mother-to-progeny) transmission.

Geographical distribution

Members of the genus Muscavirus have a global distribution, being found in North America, Europe, Africa, Asia, the Caribbean, and the southwestern Pacific, corresponding to those areas that are infested by the cosmopolitan pest, the common housefly Musca domestica (Prompiboon et al., 2010).

Pathogenicity

Muscavirus infection induces extensive nuclear and cellular hypertrophy of the salivary glands (SG), thereby causing non-lytic increase in individual cell sizes (without an increase in cell numbers), and ultimately, the SGs are hypertrophic (i.e. enlarged cells incapable of dividing) (Figure 4A.Hytrosaviridae and 4B.Hytrosaviridae) (Kariithi et al., 2017a, Lietze et al., 2011c, Lietze et al., 2011a). Infection by muscavirus induces overt SGH symptoms in 100% of flies (i.e. the virus does not infect asymptomatically) within 3 days post-infection (Lietze et al., 2007). However, adult flies develop resistance to oral infection within hours after eclosion, potentially due to the maturation of the peritrophic membrane (Lietze et al., 2011b, Boucias et al., 2015). Post-challenge, the virus replicates rapidly and completely shuts down vitellogenesis, potentially via blocking production of sesquiterpenoids (Kariithi et al., 2017b, Lietze et al., 2007). Infection by muscavirus alters housefly mating behaviors; viremic females refuse to copulate when paired with healthy males, while viremic males show reduced avidity to initiate courtship with healthy females (Kariithi et al., 2017b, Lietze et al., 2007). Females infected at a previtellogenic stage neither mate nor develop eggs, while those infected at postvitellogenic stage deposit their current egg batches only. However, the infected flies do not exhibit any external disease signs (Lietze et al., 2007). The mechanism underlying the cytopathology exhibited by the infected SGs cells is unknown, and the majority of the 108 muscavirus genes have no known homologs (Salem et al., 2009). However, ORF78 encodes a homolog of the baculovirus inhibitor of apoptosis (iap), which may be involved in the prevention of programmed cell death, thus allowing the persistence of non-lytic SGH throughout the adult housefly lifespan serving as a foci for production of progeny virus (Lietze et al., 2011c).

Species demarcation criteria

Species demarcation criteria have not been defined yet since Musca hytrovirus is the only species in the genus Muscavirus. Up to 16 different muscavirus isolates have been reported from several ecogeographical regions (Prompiboon et al., 2010, Geden et al., 2011b), but they have not been characterized.

Member species

Species Virus name(s) Exemplar isolate Exemplar accession number Exemplar RefSeq number Available sequence Other isolates Other isolate accession numbers Virus abbreviation Isolate abbreviation
Musca hytrovirus Musca domestica salivary gland hypertrophy virus EU522111 NC_010671 Complete genome MdSGHV
Virus names, the choice of exemplar isolates, and virus abbreviations, are not official ICTV designations.

Related, unclassified viruses

Virus name

Accession number

Virus abbreviation

Merodon equestris salivary gland hypertrophy virus1

 

MeSGHV

Virus names and virus abbreviations are not official ICTV designations.

Authors: Hytrosaviridae

Henry M. Kariithi †
Biotechnology Research Institute
Kenya Agricultural and Livestock Research Organization
Kaptagat Road, Loresho
P. O Box 57811
Nairobi 00200
Kenya
E-mail: henry.kariithi@kalro.org

† Current Address:
Southeast Poultry Research Laboratory
United States National Poultry Research Center
USDA-ARS
934 College Station Road
Athens, GA 30605
USA
Tel: +1(706)-521-9021
E-mail: henry.kariithi@ars.usda.gov

Just M. Vlak
Laboratory of Virology
Wageningen University & Research
Droevendaalsesteeg 1
Wageningen 6708 PB
The Netherlands
Tel: +31 317483090
E-mail: just.vlak@wur.nl

Johannes A. Jehle
Institute for Biological Control
Federal Research Centre for Cultivated Plants
Julius Kühn‐Institut
Heinrichstraße 243
64287 Darmstadt
Germany
Tel: +49 (0)6151 407 220
E-mail johannes.jehle@julius-kuehn.de

Max Bergoin
Laboratoire de Pathologie Comparée
Faculté des Sciences
Université de Montpellier
Montpellier 34095
France
Tel: +33 (0) 683 117 927
E-mail: max.bergoin@umontpellier.fr

Drion G. Boucias
Entomology and Nematology Department
University of Florida
970 Natural Area Drive
Gainesville
Florida 32611-0620
USA
Tel: +1 352-392-1901-147
E-mail: pathos@ufl.edu

Adly M. M. Abd-Alla*
Insect Pest Control Laboratory
Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture
Department of Nuclear Applications
International Atomic Energy Agency
P.O. Box 100
A-1400 Vienna
Austria
Tel: +43-1 2600-28425
E-mail: a.m.m.abd-Alla@iaea.org

* to whom correspondence should be addressed


Resources: Hytrosaviridae


References: Hytrosaviridae

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Citation: Hytrosaviridae

A summary of this ICTV Report chapter has been published as an ICTV Virus Taxonomy Profile article in the Journal of General Virology, and should be cited when referencing this online chapter as follows:

Henry M. Kariithi, Just M. Vlak, Johannes A. Jehle, Max Bergoin, Drion G. Boucias, Adly M. M. Abd-Alla, and ICTV Report Consortium, 2019, ICTV Virus Taxonomy Profile: Hytrosaviridae, Journal of General Virology, 100, 12711272.