Abstract
Hytrosaviridae is a family of large, rod-shaped, enveloped entomopathogenic viruses with dsDNA genomes of 120–190 kbp. Hytrosaviruses (also known as salivary gland hypertrophy viruses) primarily replicate in the salivary glands of adult dipteran flies. Hytrosaviruses infecting the haematophagous tsetse fly and the filth-feeding housefly are assigned to two genera, Glossinavirus and Muscavirus, respectively. Whereas muscavirus infections are only overt, glossinavirus infections can be either covert or overt. Overt infections are characterized by diagnostic salivary gland hypertrophy and cause either partial or complete infertility. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hytrosaviridae, which is available at ictv.global/report/hytrosaviridae.
Keywords: Hytrosaviridae, ICTV Report, taxonomy
VIRION
Hytrosaviruses have non-occluded, enveloped, rod-shaped virions measuring 50–80×500–1000 nm, which contain a thin, dense, central nucleocapsid encasing the DNA–protein core (Table 1, Fig. 1) [1,4]. The outer surface of glossinavirus virions 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). A 10 nm-thick amorphous proteinaceous tegument surrounds the 40 nm diameter helical nucleocapsid core underlying the virus envelope [3,4]. Muscavirus virions contain regularly braided, bead-like surface projections [2,5].
Table 1. Characteristics of members of the family Hytrosaviridae.
| 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, 120–190 kbp, encoding 108–174 proteins |
| Replication | DNA synthesis and transcription within nuclear replication complexes; temporal expression of genes |
| Translation | Presumably via cap-dependent, polyadenylated monocistronic mRNAs |
| Host range | Dipterans: tsetse fly (Glossinavirus); housefly and stable fly (Muscavirus) |
| Taxonomy | Two genera (Glossinavirus and Muscavirus) |
Fig. 1. Transmission electron micrographs showing the structural features of Glossina pallidipes salivary gland hypertrophy virus – Uganda strain; inset – cross-section. Adapted from [5].

Genome
Hytrosaviruses contain large, supercoiled, circular dsDNA genomes of 120–190 kbp with 108–174 putative, non-overlapping genes that are evenly distributed over both DNA strands in unidirectional clusters (Fig. 2) [6]. The transcription elements of the muscavirus genome are largely unknown, but the majority of the ORFs are enriched with TAAG motifs, poly(A) signals and TATA box elements [5]. At least 61 glossinavirus ORFs and 29 muscavirus ORFs are known to encode virion proteins.
Fig. 2. 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. The letters on the innermost ring represent BglII restriction fragments. Green boxes indicate the position of direct repeat sequences. Information derived from [6].

Replication
Hytrosaviruses primarily replicate in virogenic stroma in the nuclei of salivary gland cells, and in non-salivary gland tissues (e.g. tracheal cells, milk glands, corpora allata/cardiaca). Following internalization, capsids are released into the cytoplasm and traffic to the cell nucleus, where gene transcription, DNA replication and nucleocapsid assembly in the virogenic stroma occurs [4,7]. Virus replication is thought to involve the expression of immediate early (transcription factor), early (DNA replication) and late (structural protein) genes [4,5]. Nucleocapsids exit the nucleus via the nuclear pore complex and acquire envelopes in the cytoplasm; mature particles egress by budding through (muscavirus virions) or lysis (glossinavirus virions) of the luminal membranes of infected cells [4,5]. Replication in non-salivary gland tissues causes partial sterility (in tsetse fly) and complete shutdown of vitellogenesis (in housefly) [8]. Hytrosaviruses presumably produce capped, polyadenylated, monocistronic mRNAs, and possibly use cap-dependent translation [4,6].
Taxonomy
Two species in two genera have been described: Glossina hytrovirus in Glossinavirus and Musca hytrovirus in Muscavirus [1]. A future Taxonomic Proposal will seek to align the spelling of species names with that of the family. A related, unclassified virus infects the phytophagous syrphid fly, Merodon equestris [9]. Phylogenetic analysis of virus DNA polymerases indicates clearly that members of the Hytrosaviridae are distant from other viruses with large DNA genomes.
Resources
Full ICTV Report on the family Hytrosaviridae: ictv.global/report/hytrosaviridae.
Acknowledgements
Members of the ICTV (10th) Report Consortium are Elliot J. Lefkowitz, Andrew J. Davison, Stuart G. Siddell, Peter Simmonds, Sead Sabanadzovic, Donald B. Smith, Richard J. Orton and Balázs Harrach.
Footnotes
Funding: Production of this summary, the online chapter, and associated resources was funded by a grant from the Wellcome Trust (WT108418AIA).
Contributor Information
Henry M. Kariithi, Email: henry.kariithi@kalro.org; henry.kariithi@ars.usda.gov.
Just M. Vlak, Email: just.vlak@wur.nl.
Johannes A. Jehle, Email: johannes.jehle@julius-kuehn.de.
Max Bergoin, Email: max.bergoin@umontpellier.fr.
Drion G. Boucias, Email: pathos@ufl.edu.
Adly M. M. Abd-Alla, Email: a.m.m.abd-alla@iaea.org.
References
- 1.Abd-Alla AM, Vlak JM, Bergoin M, Maruniak JE, Parker A, et al. Hytrosaviridae: a proposal for classification and nomenclature of a new insect virus family. Arch Virol. 2009;154:909–918. doi: 10.1007/s00705-009-0398-5. [DOI] [PubMed] [Google Scholar]
- 2.Garcia-Maruniak A, Abd-Alla AM, Salem TZ, Parker AG, Lietze VU, et al. Two viruses that cause salivary gland hypertrophy in Glossina pallidipes and Musca domestica are related and form a distinct phylogenetic clade. J Gen Virol. 2009;90:334–346. doi: 10.1099/vir.0.006783-0. [DOI] [PubMed] [Google Scholar]
- 3.Orlov I, Drillien R, Spehner D, Bergoin M, Abd-Alla AM, et al. Structural features of the salivary gland hypertrophy virus of the tsetse fly revealed by cryo-electron microscopy and tomography. Virology. 2018;514:165–169. doi: 10.1016/j.virol.2017.11.016. [DOI] [PubMed] [Google Scholar]
- 4.Kariithi HM, van Lent JW, Boeren S, Abd-Alla AM, Ince IA, et al. Correlation between structure, protein composition, morphogenesis and cytopathology of Glossina pallidipes salivary gland hypertrophy virus. J Gen Virol. 2013;94:193–208. doi: 10.1099/vir.0.047423-0. [DOI] [PubMed] [Google Scholar]
- 5.Kariithi HM, Meki IK, Boucias DG, Abd-Alla AM. Hytrosaviruses: current status and perspective. Curr Opin Insect Sci. 2017;22:71–78. doi: 10.1016/j.cois.2017.05.009. [DOI] [PubMed] [Google Scholar]
- 6.Abd-Alla AM, Kariithi HM, Cousserans F, Parker NJ, İnce IA, et al. Comprehensive annotation of Glossina pallidipes salivary gland hypertrophy virus from Ethiopian tsetse flies: a proteogenomics approach. J Gen Virol. 2016;97:1010–1031. doi: 10.1099/jgv.0.000409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kariithi HM, Ince IA, Boeren S, Abd-Alla AM, Parker AG, et al. The salivary secretome of the tsetse fly Glossina pallidipes (Diptera: Glossinidae) infected by salivary gland hypertrophy virus. PLoS Negl Trop Dis. 2011;5:e1371. doi: 10.1371/journal.pntd.0001371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Kariithi HM, Yao X, Yu F, Teal PE, Verhoeven CP, et al. Responses of the Housefly, Musca domestica, to the Hytrosavirus Replication: Impacts on Host's Vitellogenesis and Immunity. Front Microbiol. 2017;8:583. doi: 10.3389/fmicb.2017.00583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Amargier A, Lyon JP, Vago C, Meynadier G, Veyrunes JC. [Discovery and purification of a virus in gland hyperplasia of insects. Study of Merodon equistris F. (Diptera, Syrphidae)] C R Seances Acad Sci D. 1979;289:481–484. [PubMed] [Google Scholar]
