Una Virus

Una virus (UNAV; species Alphavirus una) is an enveloped, positive-sense, single-stranded RNA arbovirus in the genus Alphavirus (family Togaviridae). Within the Semliki Forest antigenic complex, Una virus represents the closest phylogenetic and antigenic sister species to Mayaro virus, sharing 73 to 77 percent nucleotide identity and 83 to 86 percent amino acid identity across its structural and nonstructural open reading frames. Despite this close evolutionary affinity, Una virus exhibits a distinct transmission ecology: whereas Mayaro virus is maintained in a rainforest canopy cycle between arboreal Haemagogus janthinomys mosquitoes and non-human primates, Una virus circulates at ground level in flooded forests, gallery savannas, and seasonal wetlands through floodwater mosquitoes—principally Psorophora ferox and Aedes (Ochlerotatus) species—feeding on terrestrial mammals and birds.

First isolated in 1959 near Belém, Pará, Brazil, Una virus is distributed across an expansive latitudinal corridor stretching from Panama, Trinidad, and the Guiana Shield through the Amazon and Orinoco river basins into the Pantanal wetlands and the subtropical Gran Chaco of northern and central Argentina.

The 1959 Belém Isolation

Una virus was discovered in May 1959 by Otis R. Causey, Calista E. Causey, O. M. Maroja, and Darcy G. Macedo during arboviral surveillance conducted by the Belém Virus Laboratory in Belém, Pará, Brazil. The prototype strain (BeAr 13136) was isolated from a pool of diurnal ground-pool mosquitoes identified as Psorophora ferox collected in secondary forest along the Una Highway (Rodovia do Una) in Belém. Inoculated intracerebrally into newborn Swiss mice, the suspension produced fatal encephalitis within 48 to 72 hours. Complement-fixation and hemagglutination-inhibition assays placed strain BeAr 13136 in Casals' Group A arboviruses (genus Alphavirus), closely allied to the 1954 Trinidad prototype of Mayaro virus but separable by neutralization.

Species Recognition Within the Genus Alphavirus

Initially treated in some catalogs as a subtype of Mayaro virus, Una virus was elevated to an independent species (Alphavirus una) by the International Committee on Taxonomy of Viruses (ICTV) on the basis of fourfold or greater two-way neutralization differences and over 20 percent nucleotide divergence across the structural polyprotein gene. Together, Mayaro virus and Una virus form a monophyletic South American subclade within the Semliki Forest antigenic complex.

Envelope Glycoprotein Shell and Nucleocapsid Core

The mature Una virion is an icosahedral, spherical particle ~70 nanometers in diameter with T = 4 quasi-equivalence. The nucleocapsid core contains a single copy of genomic RNA complexed with 240 copies of the basic capsid protein (C, ~30 kDa), enclosed by a host-derived lipid bilayer containing 240 heterodimers of transmembrane glycoproteins E1 (~48 kDa) and E2 (~47 kDa) arranged into 80 trimeric spikes. Surface domains of E2 mediate receptor attachment, whereas E1 contains the hydrophobic class II fusion peptide triggered by endosomal acidification.

Genomic Organization and Polyproteins

The Una virus genome is a non-segmented, positive-sense single-stranded RNA molecule of ~11,450 nucleotides bearing a 5' methylated cap (m⁷GpppA) and a 3' poly(A) tract, organized into two open reading frames (ORFs):

Comparative sequencing of the E1, E2, and nsP1 genes by Ann M. Powers and colleagues (2006) demonstrated that Una virus displays pronounced regional genetic subdivision across three biogeographical clades:

1. Amazon Basin and Guiana Shield (UNAV Clade I): Encompasses the 1959 Belém prototype (BeAr 13136) and strains isolated across Pará and Amazonas states in Brazil, French Guiana, Suriname, and the Peruvian Amazon.
2. Venezuelan and Colombian Llanos & Isthmian Clade (UNAV Clade II): Includes strains recovered from seasonal flooded savannas in Venezuela (Zulia, Cojedes, and Barinas), Colombia (Meta and Casanare), Trinidad, and Panama.
3. Southern Cone, Pantanal, and Argentine Chaco Clade (UNAV Clade III): Represents a southern lineage isolated from mosquitoes, sentinel horses, and wild vertebrates across the Brazilian Pantanal (Mato Grosso do Sul) and the subtropical Gran Chaco and Pampas eco-regions of Argentina (Chaco, Corrientes, Santa Fe, Córdoba, and Tucumán provinces).

Whereas Mayaro virus strains from distant Amazonian sites cluster closely due to continuous canopy connectivity, Una virus lineages show strong geographic clustering by river basin and savanna corridor, reflecting localized maintenance by terrestrial hosts and ground-pool floodwater mosquitoes.

Floodwater Mosquito Vectors: Psorophora ferox and Aedes Species

Field entomology indicates that Psorophora ferox is the primary vector of Una virus across tropical and subtropical South America. Psorophora ferox is a multivoltine floodwater mosquito whose drought-resistant eggs are deposited in moist depressions on the forest floor or seasonal savanna margins, hatching synchronously after heavy rainfall inundates temporary pools. Adult females rest in low vegetation and bite mammalian and avian hosts at ground level during daytime and crepuscular hours. Additional field isolations have been obtained from ground-feeding Aedes (Ochlerotatus) species—including Aedes serratus, Aedes fulvus, and Aedes scapularis—as well as Psorophora albipes, Coquillettidia arribalzagae, and Culex (Melanoconion) species.

Mammalian and Avian Vertebrate Hosts

Because Psorophora and Aedes ground-pool vectors are generalist feeders, Una virus circulates across diverse terrestrial vertebrates and birds:

• Equids and Domestic Ungulates: Seroepidemiological surveys in the Argentine Chaco, Santa Fe, and the Brazilian Pantanal consistently detect neutralizing antibodies against Una virus in domestic horses (Equus caballus) and cattle.
• Non-Human Primates and Forest Mammals: Neutralizing antibodies occur in black-and-gold howler monkeys (Alouatta caraya) in northeastern Argentina and southern Brazil, capuchin monkeys (Sapajus spp.), peccaries (Tayassu pecari), capybaras (Hydrochoerus hydrochaeris), and terrestrial rodents (Proechimys and Oryzomys spp.).
• Avian Hosts: Virus isolations and neutralizing titers in resident passerines, columbiform doves, and wading birds in Venezuela, Brazil, and Argentina indicate that ground-foraging birds contribute to dispersal between wetland patches.

Human infections with Una virus are documented primarily through seroprevalence surveys in rural forest-edge, riverine, and agricultural populations in Brazil, Peru, Venezuela, French Guiana, and Argentina, where neutralizing antibody prevalence ranges from 2 to 18 percent. Symptomatic human cases identified during febrile surveillance present with mild-to-moderate acute febrile illness, headache, myalgia, and transient arthralgia, without the prolonged chronic polyarthritis characteristic of Mayaro fever or chikungunya.

Reference laboratories rely on two diagnostic methods:

1. Cross-Comparative Plaque Reduction Neutralization Test (PRNT₈₀ / PRNT₉₀): Because antibodies elicited by Una virus cross-react with Mayaro and chikungunya viruses in standard IgM/IgG ELISA and hemagglutination-inhibition assays, definitive serodiagnosis requires parallel neutralization testing demonstrating a fourfold or greater titer differential against Una virus.
2. Species-Specific RT-qPCR: Real-time reverse transcription PCR primers targeting divergent regions of the nsP1 and E2 genes distinguish Una virus RNA in acute serum or field-collected mosquito pools.

Why do Mayaro virus and Una virus have different geographic patterns despite being sister species?

Mayaro virus is maintained in a canopy cycle between Haemagogus janthinomys and arboreal primates, restricting its primary range to humid tropical rainforests. By contrast, Una virus adapted to ground-pool floodwater mosquitoes (Psorophora ferox and Aedes serratus) and terrestrial mammals, enabling it to colonize seasonally flooded savannas, gallery forests, and subtropical wetlands as far south as central Argentina.

Does Una virus cause neurological disease in horses like Venezuelan or Eastern equine encephalitis viruses?

Although horses in the Pantanal, Llanos, and Argentine Chaco frequently seroconvert to Una virus with high neutralizing antibody titers, equine infection is predominantly subclinical or associated with self-limiting fever, as Una virus belongs to the Semliki Forest complex rather than the encephalitic alphavirus clades.

1. Causey, O. R., Casals, J., Shope, R. E., & Udomsakdi, S. (1963). "Aura and Una, two new group A arthropod-borne viruses." The American Journal of Tropical Medicine and Hygiene, 12(5), 777–781. https://doi.org/10.4269/ajtmh.1963.12.777
2. Powers, A. M., Aguilar, P. V., Chandler, L. J., et al. (2006). "Genetic relationships among Mayaro and Una viruses suggest distinct patterns of transmission." The American Journal of Tropical Medicine and Hygiene, 75(3), 461–469. https://doi.org/10.4269/ajtmh.2006.75.461
3. Diaz, L. A., Spinsanti, L. I., Almiron, W. R., & Contigiani, M. S. (2003). "UNA virus: first report of human infection in Argentina." Revista do Instituto de Medicina Tropical de São Paulo, 45(2), 109–110. https://doi.org/10.1590/S0036-46652003000200012
4. Pauvolid-Corrêa, A., Juliano, R. S., Campos, Z., Velez, J., Nogueira, R. M. R., & Komar, N. (2015). "Neutralising antibodies for Mayaro and Una viruses in Pantanal, Brazil: first evidence of Una virus circulation in domestic horses and free-ranging caimans." Memórias do Instituto Oswaldo Cruz, 110(1), 119–123. https://doi.org/10.1590/0074-02760140383