Evolution of Viruses - Zhdanov V. M. 1990

Special Section
Arenaviruses

The Arenaviridae family unites a clearly defined group of Viruses. Most of these viruses cause severe hemorrhagic fevers, are transmitted without Blood-sucking Arthropods, and share serological relationships. A small number of representatives (13 viruses) of this family are grouped into a single genus (Arenavirus).

Arenavirus virions are 110–130 nm in size, consisting of a core (nucleocapsid) and an outer envelope with 10 nm long projections. One or several host Cell Ribosomes—"sand grains" (arena)—are found inside the envelope. Virion RNA is represented by two virus-specific fragments with a molecular mass of 1.1x10⁶— 1.6x10⁶(5) and 2.1x10⁶—3.2x10⁶(L). In addition, virions contain 3 ribosomal RNA fragments: 28S, 18S, and 4–6S [Leung W. et al., 1981]. Virion L and S-RNAs contain similar sequences about 30 NUCLEOTIDES in length at the 3'- and 5'-ends of the molecule. Virions include an non-glycosylated protein (63,000—72,000) forming the ribonucleoprotein, and two glycosylated Proteins GP1 (54,000—72,000) and GP2 (34,000—44,000). Their synthesis is encoded by the S-RNA fragment. Virions also contain transcriptase and poly(U)—poly(A) polymerases. A specific feature of arenavirus Gene METABOLISM/31.html">Transcription is the bipolarity of the S-RNA fragment: half of it adjacent to the 5'-end has negative polarity, while the second half has positive polarity, and they are separated by a hairpin. Therefore, mRNA for protein N is transcribed from the virion RNA, whereas the second, non-structural protein is transcribed from the right half of its complementary copy. Replication occurs, as in negative-sense viruses, in two stages: first, a full complementary strand is synthesized, followed by daughter RNAs.

Following adsorption onto cell Membrane Receptors, virions penetrate Cells via viropexis, accompanied by the fusion of cellular and viral membranes and the release of the nucleoprotein, which begins functioning in the Cytoplasm. Transcribed genes function as mRNA, encoding the synthesis of viral proteins. Subsequently, virion daughter RNAs are synthesized, capsids are assembled, and virions are formed, leaving The Cell by budding.

The number of species belonging to the family, which constitute the single genus Arenavirus, is small (13). Under natural conditions, all of them infect rodents, causing persistent infection. Along with horizontal transmission, vertical transmission also exists. Although arenavirus replication in ticks has been demonstrated in experiments, arenaviruses spread without vectors (Table 14). At least 4 representatives of this family cause severe diseases typically accompanied by a hemorrhagic syndrome: lymphocytic choriomeningitis (LCM), Lassa, Machupo, and Junin fevers. All arenaviruses are causative agents of persistent, partially asymptomatic infections in rodents. Only the Tacaribe virus has been isolated from bats and mosquitoes In addition to rodents. Perhaps these fevers are incidental [Murphy F., 1977].

Endemic foci are currently located in the equatorial, subequatorial, tropical, and subtropical climatic zones. An exception is lymphocytic choriomeningitis (see below). Arenaviruses are widely distributed in nature among both wild and semi-synanthropic rodents (grassland forms). The latter are precisely the cause of disease outbreaks among humans. This occurs As a result of seasonal rodent Migrations into human dwellings (Lassa fever, Bolivian hemorrhagic fever) or during agricultural work (harvesting maize in Argentine hemorrhagic fever foci). The incidence is seasonal. After rodents leave or are exterminated, the diseases cease. Among rodents, the virus spreads both horizontally and vertically [Rawls W., Leung W., 1978]. Humans become infected via food, Water, air, and damaged Skin areas contaminated with rodent excreta (mainly urine).

The formation of arenaviruses presumably "originated" in the Paleocene, when a connection existed between South America and Africa. Experiments have shown a high frequency of recombination with tc-mutants of the Pichinde virus. The Role of recombination in evolution cannot be ruled out, although the likelihood of two different arenaviruses replicating within the Organism of a single rodent is low. The rather strict restriction of various arenaviruses to specific rodent species should be taken into account.

Table 14. Distribution of arenaviruses and their association with rodents

In South America, arenaviruses are ecologically associated with a single tribe of the family Cricetidae, which migrated to South America from North America during the Miocene–Pliocene. This process was accompanied by active speciation. The Emergence of South American arenavirus species is possibly linked to this period [Calosher C., 1980]. The appearance of the Tamiami arenavirus in North America (Florida) appears to be of secondary origin. The virus parasitizes *Sigmodon hispidus*, which are of South American origin dating back to the Pleistocene with secondary penetration through Central America into the southern parts of North America [Arata A., Gratz M., 1975].

The primary natural reservoir of the African Lassa arenavirus is the natal multimammate mouse (*Praomys [mastomys] natalensis*), which occupies a taxonomic position intermediate between the house mouse and the ship (black) Alexandrine rat. These rodents inhabit the savanna zone south of the Sahara. On the African continent, this is the most widespread and abundant species inhabiting bushes and cultivated fields, easily moving from human dwellings to wild rodent habitats. The species traces its origins to the Pleistocene and emerged during successive periods of isolation in savanna-to-forest transition zones [Bellier, 1975]. In the Old World, arenaviruses are associated with one of 6 subfamilies of Muridae. Both of these Old and New World rodent groups are the most numerous and viable, dominating other rodents in terms of population within their ranges [Arata A., Gratz M., 1975]. Long-term ecological relationships likely exist between South American arenaviruses and a group of closely related rodents from the genera Oryzomys, Calomys, Akodon, Neacomys, Thomasomys, Sigmodon.

The speciation of the LCM virus is likely associated with The Development of human society and the widespread distribution of house mice. Until the early 1970s, this mouse species was considered the sole reservoir of the virus. However, in recent decades, A number of outbreaks have been described in humans infected from captive Syrian hamsters that had suffered from LCM, mostly as a persistent infection, sometimes clinically overt. Natural foci of LCM remain practically unstudied. There are known cases of virus isolation from the wood mice Apodemus sylvaticus and *A. flavicollis* [Lehmann-Grube F. et al., 1971]. The genus Apodemus is taxonomically close to the genus Mus and belongs to Palearctic forms. The original ranges of these genera partially overlap. The ancestral homeland of house mice is Central Asia, where the currently surviving natural foci of LCM should probably be sought. From the center of formation, the species spread in two directions—northwest (*Mus musculus musculus*) and southwest (*Mus musculus domesticus*). These populations currently do not interbreed, but both serve as carriers of LCM. Their initial infection likely occurred in the center of speciation—in the southern Central Asian region.