2024 taxonomy update for the family Retroviridae

Abstract

The Retroviridae are a family of viruses that reverse transcribe their RNA genome and integrate the resulting double-stranded DNA copy into the genome of the host cell. Retroviruses are well-documented pathogens that have been associated with a variety of diseases. The International Committee on Taxonomy of Viruses (ICTV) currently lists 65 species of retroviruses. As required by the ICTV, we have converted the species nomenclature to a binomial format comprised of the genus and a freeform epithet. Assigning binomial species names to classify new retroviruses will be facilitated when following the epithet rules described herein.

Introduction

The Retroviridae are a taxonomic family within the order Ortervirales, which includes five families of reverse-transcribing viruses [4]. The International Committee on Taxonomy of Viruses (ICTV) currently lists 65 retrovirus species within the genera Alpharetrovirus, Betaretrovirus, Deltaretrovirus, Epsilonretrovirus, Gammaretrovirus, Lentivirus, Bovispumavirus, Equispumavirus, Felispumavirus, Prosimiispumavirus, and Simiispumavirus. Spumaviruses, commonly referred to as foamy viruses, are grouped in the taxonomic subfamily Spumaretrovirinae, while all other retroviruses are grouped in the subfamily Orthoretrovirinae.

The genome of viruses in the subfamily Orthoretrovirinae is a dimer of linear, single-stranded, positive-sense RNA molecules (ssRNA) ranging between approximately 7 kb and 13 kb in length (Fig. 1). The ssRNA strands are reverse transcribed into dsDNA by retrovirus-encoded reverse transcriptase (RT), a process primed by a free 3’-hydroxyl group of a specific tRNA bound to the primer binding site (PBS) of the retroviral RNA. The resulting dsDNA (proviral DNA precursor) is integrated into the genomic DNA of the infected cell by the retrovirus-encoded integrase (IN). The genome-integrated retroviral dsDNA copy is referred to as a “provirus”. Long terminal repeats (LTRs) comprise the 5’ and 3’ boundaries of the provirus and flank open reading frames that always include the genes gag, encoding the virion structural protein precursor (Gag, processed into matrix [MA], capsid [CA] and nucleocapsid [NC] proteins, and various other proteins), pro, encoding the protease (PR), pol, encoding the other virion proteins with enzymatic activities (RT, IN, and RNase H), and env, encoding the Env proteins – surface (SU) and transmembrane (TM). In some retroviruses, the protease is part of the Pol polyprotein. A few retroviruses also encode a dUTPase within the gag or pol reading frame. More-complex retroviruses encode accessory proteins between pol and the 3’LTR. In addition, some retrovirus isolates (indicated by “**” in Table 1) contain a host-cell-derived oncogene whose expression can lead to transformation of an infected cell into a cancer cell. Since retroviral oncogenes usually replace a viral sequence that is essential for replication, such viruses can be transmitted in a mixture with a non-defective helper virus that provides the missing functions.

Fig. 1.

Schematic depiction of representative retroviral genomes. Proviruses and their encoded genes are depicted for the gammaretrovirus Moloney murine leukemia virus (species Gammaretrovirus murleu) and the lentivirus human immunodeficiency virus 1 (species Lentivirus humimdef1) as examples of simple and complex retroviral genomes, respectively. In addition, a representative proviral genome of the simiispumavirus simian foamy virus (Simiispumavirus sp.), containing an internal promoter (IP) driving accessory gene expression, is depicted

Table 1.

ICTV-approved binomial species names for retroviruses included in the ICTV master species list^*

Species name	Exemplar virus name	Virus name abbreviation	Exemplar GenBank accession number
Alpharetrovirus avicarmilhil2	avian carcinoma Mill Hill virus 2**	AMV2	M14008
Alpharetrovirus avifujsar	Fujinami sarcoma virus**	FuSV	AF033810
Alpharetrovirus avileu	avian leukosis virus	ALV	M37980
Alpharetrovirus avimyebla	avian myeloblastosis virus**	AMV	J02013
Alpharetrovirus avimyecyt29	avian myelocytomatosis virus 29**	AMV29	AF033809
Alpharetrovirus avirousar	Rous sarcoma virus**	RSV	AF033808
Alpharetrovirus avisar10	avian sarcoma virus CT10**	ASVCT10	Y00302
Alpharetrovirus aviUR2sar	UR2 sarcoma virus**	UR2SV	M10455
Alpharetrovirus aviY73sar	Y73 sarcoma virus**	Y73SV	L21974
Betaretrovirus lan	Langur virus	LNGV	AY282754
Betaretrovirus maspfimon	Mason-Pfizer monkey virus	MPMV	AF033815
Betaretrovirus murmamtum	mouse mammary tumor virus	MMTV	AF033807
Betaretrovirus ovijaa	Jaagsiekte sheep retrovirus	JSRV	M80216
Betaretrovirus squmon	squirrel monkey retrovirus	SMRV	M23385
Deltaretrovirus bovleu	bovine leukemia virus	BLV	AF033818
Deltaretrovirus priTlym1	primate T-lymphotropic virus 1	PTLV1	AF074966
Deltaretrovirus priTlym2	primate T-lymphotropic virus 2	PTLV2	M10060
Deltaretrovirus priTlym3	primate T-lymphotropic virus 3	PTLV3	AF391797
Epsilonretrovirus waldersar	walleye dermal sarcoma virus	WDSV	AF033822
Epsilonretrovirus walepihyp1	walleye epidermal hyperplasia virus 1	WEHV1	AF014792
Epsilonretrovirus walepihyp2	walleye epidermal hyperplasia virus 2	WEHV2	AF014793
Gammaretrovirus aviretend	reticuloendotheliosis virus**	REV	AY842951
Gammaretrovirus avisplnec	Trager duck spleen necrosis virus	TDSNV	X02759
Gammaretrovirus chisyn	chick syncytial virus	CSV	DQ237904
Gammaretrovirus felleu	feline leukemia virus	FeLV	AF052723
Gammaretrovirus fibijimursar	Finkel-Biskis-Jinkins murine sarcoma virus**	FBJMSV	K02712
Gammaretrovirus gibleu	gibbon ape leukemia virus	GALV	M26927
Gammaretrovirus Hamursar	Harvey murine sarcoma virus**	HaMSV	J02207
Gammaretrovirus hazufelsar	Hardy-Zuckerman feline sarcoma virus**	HZFeSV	X03711
Gammaretrovirus Kimursar	Kirsten murine sarcoma virus**	KiMSV	X00984
Gammaretrovirus koa	koala retrovirus	KoRV	AF151794
Gammaretrovirus momursar	Moloney murine sarcoma virus**	MoMSV	AF033813
Gammaretrovirus murleu	Moloney murine leukemia virus	MMLV	AF033811
Gammaretrovirus porConc	porcine type-C oncovirus	PCOV	AF356697
Gammaretrovirus snythefelsar	Snyder-Theilen feline sarcoma virus**	STFeSV	M22820
Gammaretrovirus woomonsar	woolly monkey sarcoma virus	WMSV	V01201
Lentivirus bovimdef	bovine immunodeficiency virus	BIV	M32690
Lentivirus bovjem	Jembrana disease virus	JDV	U21603
Lentivirus capartenc	caprine arthritis encephalitis virus	CAEV	M33677
Lentivirus equinfane	equine infectious anemia virus	EIAV	U01866
Lentivirus felimdef	feline immunodeficiency virus	FIV	M25381
Lentivirus humimdef1	human immunodeficiency virus 1	HIV-1	AF033819
Lentivirus humimdef2	human immunodeficiency virus 2	HIV-2	M30502
Lentivirus ovivismae	visna/maedi virus	VMV	L06906
Lentivirus pum	puma lentivirus	PLV	U03982
Lentivirus simimdef	simian immunodeficiency virus	SIV	M58410
Bovispumavirus bostau	bovine foamy virus Bos taurus	BFVbta	U94514
Equispumavirus equcab	equine foamy virus Equus caballus	EFVeca	AF201902
Felispumavirus felcat	feline foamy virus Felis catus	FFVfca	Y08851
Prosimiispumavirus otocra	simian foamy virus Otolemur crassicaudatus	SFVocr	KM233624
Simiispumavirus atespp	simian foamy virus Ateles spp.	SFVa	EU010385
Simiispumavirus caljac	simian foamy virus Callithrix jacchus	SFVcja	GU356395
Simiispumavirus cernic	simian foamy virus Cercopithecus nictitans	SFVcni	JQ867466
Simiispumavirus chlaet	simian foamy virus Chlorocebus aethiops	SFVcae	M74895
Simiispumavirus gorgorgor	simian foamy virus Gorilla gorilla gorilla	SFVggo	HM245790
Simiispumavirus maccyc	simian foamy virus Macaca cyclopis	SFVmcy	X54482
Simiispumavirus macfas	simian foamy virus Macaca fascicularis	SFVmfa	LC094267
Simiispumavirus macfus	simian foamy virus Macaca fuscata	SFVmfu	AB923518
Simiispumavirus macmul	simian foamy virus Macaca mulatta	SFVmmu	MF280817
Simiispumavirus pantrosch	simian foamy virus Pan troglodytes schweinfurthii	SFVpsc	KX087159
Simiispumavirus pantrotro	simian foamy virus Pan troglodytes troglodytes	SFVptr	JQ867463
Simiispumavirus pantrover	simian foamy virus Pan troglodytes verus	SFVpve	U04327
Simiispumavirus ponpygpyg	simian foamy virus Pongo pygmaeus pygmaeus	SFVppy	AJ544579
Simiispumavirus saisci	simian foamy virus Saimiri sciureus	SFVssc	GU356394
Simiispumavirus sapxan	simian foamy virus Sapajus xanthosternos	SFVsxa	KP143760

^*Note that three retrovirus species, specifically Gardner-Arnstein feline sarcoma virus, guinea pig type-C oncovirus, viper retrovirus, were abolished and removed from the Master Species List due to a current lack of sufficient sequence information for their exemplar virus isolates.

^**Retrovirus isolates containing a host cell-derived oncogene.

Transcription by RNA polymerase II is initiated within the proviral 5’LTR and terminated by polyadenylation within the proviral 3’LTR. Transcribed RNA has a cap at the 5’ end and can be spliced or remain unspliced. In the case of simple retroviruses, a single splice event produces an ENV-encoding mRNA, and in the case of more-complex retroviruses, additional splice events within the pol–env–3’LTR region produce different mRNAs for accessory proteins. Unprocessed Gag proteins translated from unspliced proviral mRNA bind provirus-transcribed, unspliced dimeric RNA, thus packaging two full-length retroviral RNA genomes into particles that also include RT and IN proteins, as well as a specific tRNA bound to the PBS. The Gag protein forms the internal structure of the virion after being processed into MA, CA, and NC domains by the viral PR following budding of the retroviral particle, a process termed “maturation”. Budding of viral particles occurs at the plasma membrane, concomitant with assembly, resulting in enveloped virions. The retroviral virion is decorated by trimeric Env proteins, each comprising three copies of SU and TM subunits (cleaved from the Env precursor) and incorporated in its plasma membrane. When infecting another cell, SU binds to specific receptors on the cell surface, resulting in TM-mediated fusion of the virion and cellular plasma membranes and transfer of the retroviral capsid into the cell cytoplasm, followed by reverse transcription of ssRNA into dsDNA (see above) and integration of the DNA into the host genome, thus completing the retroviral replication cycle [2]. Spumaretroviruses differ in some aspects of retrovirus biology. For instance, proviral transcripts can be spliced differently and, in addition, are initiated at an internal promoter located within the env gene. They also differ in the timing of reverse transcription of retroviral RNA during the replication cycle, and the envelope membrane enclosing the virion may be acquired by budding through the endoplasmic reticulum. Another difference is that the trimeric glycoprotein complex consists of three subunits: leader peptide (LP), SU, and TM [2, 5].

Many orthoretroviruses (but not spumaretroviruses) are well-documented human and veterinary pathogens that have been causally associated with a variety of diseases, including leukemias, lymphomas, sarcomas, carcinomas of mammary tissue, liver, lung, and kidney, as well as deficiencies of the immune system (e.g., AIDS), autoimmune diseases, motor neuron diseases, and acute diseases causing tissue damage [2, 6].

Due to the integration of retroviral genomes into the genome of their host cells, proviruses are occasionally formed in germ line cells of host organisms, thus becoming inheritable through generations and speciation events. Evidence of such events is found in the genomes of all vertebrates and many invertebrates, which contain considerable levels of endogenous retroviral sequences (ERVs) [1]. In the case of humans, ERVs (HERVs) and HERV-derived sequences comprise approximately 8% of the genome. Proviral sequences and ERV proteins can in some cases affect the biology of the host cell, and certain ERVs have contributed to the evolution of their host species [3, 7]. For example, Env proteins of ERVs have been exapted as syncytins, proteins that mediate fusion of adjacent cells of the trophoblast layer of the placenta to protect the mammalian fetus from maternal toxins.

Taxonomy update

In 2021, the ICTV ratified a proposal requiring all virus species names to be in a binomial format consisting of a “genus + epithet”, with various options for the style of the epithet. It is emphasized that the virus species name is different from the name of a virus; that is, the ratified proposal is not meant to eliminate the use of well-established virus names from the scientific and other literature [8–11].

Here, we provide an update for all species names in the family “Retroviridae” as reported in the current ICTV Master Species List “ICTV_Master_Species_List_2024_MSL40.v1.xlsx” (https://ictv.global/msl). In the ICTV-ratified binomial format for the family Retroviridae, the first word is the name of the genus to which the species belongs, and the epithet is derived from the virus name (Table 1; Fig. 2). Previously, species names in the family Retroviridae often consisted of multiple words and were diverse; for instance, sometimes derived from the disease caused by the virus in the host species and sometimes from the name of the discoverer/investigator of the virus. Many of those names have been in use for decades, some of them having wide use due to the high impact of the viral disease they cause, such as human immunodeficiency virus. For the sake of consistency with established virus names and to maintain brevity in species names, we decided to maintain reference to the previous names by abbreviating them in the epithets and, when applicable, to indicate the host. Therefore, the majority of species epithets begin with the first three letters of the host followed by a three-letter acronym representing the cell type, location, or disease associated with the virus based on previous virus names. An exception was made when names of discoverers/investigators were included in virus names. In those cases, the new species epithet begins with the first two or three letters of the name of the discoverer(s)/investigator(s) and taking into consideration the ease of pronunciation. In the case of foamy viruses, epithets take into account the special host-virus co-speciation and cross-species transmission and therefore incorporate the respective host’s scientific (sub)species names in an abbreviated form. In the case of spider monkey simian foamy virus, the epithet of the proposed species name includes the designation “spp” to indicate that the actual host species within genus Ateles has not been identified (Table 1).

Fig. 2.

Phylogenetic tree of retrovirus species currently listed in the ICTV taxonomy. The tree was constructed for representative members of family Retroviridae using multiple sequence alignments spanning conserved regions of the reverse transcriptase (RT) coding region of pol (domains 1–7), which is highly refractory to mutation. The RT alignment was constrained to the coordinate space of a master reference sequence (SFVpsc), with alignment columns selected based on this reference. The phylogeny was reconstructed using the maximum-likelihood method in RAxML, applying the RTrev model of amino acid substitution, selected using JModelTest. The tree is rooted on a consensus sequence for members of the subfamily Spumaretrovirinae. Asterisks indicate bootstrap support (1000 replicates) ≥ 70% for genus-level relationships and above. The scale bar represents the evolutionary distance in substitutions per site. Note that several retrovirus species listed in Table 1 are missing from the tree due to a lack of specific sequence information for the RT gene. Also note that some retroviruses are recombinants of members of different genera. For instance, Mason-Pfizer monkey virus (species Betaretrovirus maspfimon) and squirrel monkey retrovirus (species Betaretrovirus squmon) have acquired a gammaretrovirus env gene

Furthermore, in accord with the ICTV decision, we removed three retrovirus species, specifically Gardner-Arnstein feline sarcoma virus, Guinea pig type-C oncovirus, and Viper retrovirus, due to lack of sufficient sequence data.

We hope that maintaining a connection with previous virus species names in devising the binomial format for Retroviridae nomenclature will facilitate their use by our peers. Furthermore, by establishing “rules” for the selection of an epithet, assigning binomial species names to classify new retroviruses will be greatly facilitated. We would like to highlight that the virus names have not changed [11] – only species names. For example, human immunodeficiency virus type 1 is a member of the species Lentivirus humimdef1, but its name remains human immunodeficiency virus type 1.