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Alphaviruses

Viral Characteristics

In humans, the skin is a target for alphaviruses that cause a rash. The Alphavirus genus belongs to the Togaviridae family and contains ~30 virus species. They contain a +polarity single-stranded RNA genome. The genomic RNA of alphaviruses has approximately 12kb, encoding for two open-reading frames (ORFs): nonstructural and structural ORFs. The nonstructural ORF composes two-thirds of the genomic RNA, which codes for four nonstructural proteins (nsPs), namely nsP1, nsP2, nsP3, and nsP4, known to play essential roles in viral replication and enzymatic activities. The structural ORF, in contrast, encodes for six structural proteins, including capsid, E1, E2, E3, 6k, and transframe. Alphaviruses are enveloped viruses that assemble into small (~70 nm), spherical particles with T = 4 quasi-icosahedral symmetry.

The structural and genomic features of alphaviruses. Fig.1 The structural and genomic features of alphaviruses. (Weaver, 2012)

Symptom

Most alphaviruses will form plaques on susceptible mammalian or avian cells under an agar overlay. Mosquito cell lines also support replication, although often without cytopathic effect. In humans, alphaviruses can cause acute infections marked by high viremia and symptoms, including fever, rash, debilitating joint pain, encephalitis, and even morbidity. Skin rashes are observed in some alphaviruses, including Chikungunya virus (CHIKV), Barmah Forest virus (BFV), Mayaro virus (MAYV), O’nyong-nyong virus (ONNV), Ross River virus (RRV) and Sindbis (SIN).

Pathogenesis

Alphaviruses enter cells by binding proteinaceous receptors at the cell surface and undergoing clathrin-mediated endocytosis. The specific receptor that is used varies between alphavirus species. Invertebrates, initial sites of alphavirus replication include skeletal muscle, fibroblasts, osteoblasts, and macrophages in the skin, often leading to infection of the draining lymph node, allowing an efficient virus spread. Viremia is probably the main form of dissemination to other tissues and organs. Some alphaviruses such as CHIKV that cause a rash replicate in the skin and striated muscle. During infection, resident macrophages can be activated into either classically or activated macrophages depending on stimuli from the local microenvironments. Importantly, infection also triggers the recruitment of peripheral neutrophils and monocytes to the site of infection.

Schematic diagram showing skin immune sentinels and cutaneous immune response following alphavirus inoculation. Fig.2 Schematic diagram showing skin immune sentinels and cutaneous immune response following alphavirus inoculation. (Fong, 2018)

Epidemiology

  • Arthritogenic alphaviruses are globally distributed. RRV and BFV are endemic in Australia. ONNV is probably endemic in East Africa. MAYV is limited geographically to Latin America. The first local transmission of CHIKV in the Americas was identified in Caribbean countries and territories. CHIKV outbreaks had been identified in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans.
  • The human disease occurs when people intrude on enzootic foci and are bitten by infected mosquitoes. Human-to-human transmission does not occur.

Prevention and Treatment

As treatment following alphavirus infection is only supportive care (intravenous fluids, medicine to control fever and pain). No licensed human vaccines are available for alphaviruses, and control generally relies on interruption of transmission using vector control, vaccination of animal amplifying hosts, and using protection from mosquito bites.

Anti-Alphaviruses Products and Services

Alphaviruses are globally dispersed, and each continent has humans at risk. Creative Biolabs has invested generous talent and energy, and successfully constructed comprehensive technology platforms, aiming to offer the most diverse ViroAntibody products as well as convenient and extensive services to customers all over the world. We can provide customized anti-alphavirus antibodies. In addition, we also provide various assays, customized antibody discovery, and engineering services to advance your virology research. Please feel free to contact us.

References

  1. Weaver, S.C.; et al. Alphaviruses: population genetics and determinants of emergence. Antiviral Res. 2012, 94(3): 242-257.
  2. Fong, S.W.; et al. Mosquito Saliva Reshapes Alphavirus Infection and Immunopathogenesis. J Virol. 2018, 92(12).

All products and services are intended for Research Use Only, and NOT to be used in diagnostic or therapeutic procedures.

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