Pathogenicity and virulence of O’nyong-nyong virus: A less studied Togaviridae with pandemic potential

Figures & data

Figure 1. Phylogenetic tree of ONNV and other related alphaviruses. Maximum likelihood phylogenetic tree generated using alphavirus E1 sequences obtained from NCBI databases (GenBank accession numbers included in each sequence name). Sequences were aligned with MUSCLE (v3.8.31) configured for highest accuracy (default settings), ambiguous regions were removed with Gblocks (v0.91b) and HKY85 substitution model used. Only approximate likelihood-ratio tests (aLrts) higher than 0.1 are displayed.

Figure 2. Epidemiology of ONNV. Map depicting African territories with recorded outbreaks of CHIKV (coloured), ONNV (stripped) or both (coloured stripped). Individual studies reporting on ONNV outbreaks or endemic circulation are highlighted in number red dots, with details corresponding to the table provided. CHIKV endemic areas are taken from WHO ([7]).

Table 1. Reported and confirmed ONNV cases as of 2023.

Location and year	Comments	Reference
Originated in Gulu, northern Uganda and spread east and westward to Kenya, Mozambique, Senegal, Malawi, Tanzania, Cameroon, Central African Republic, Democratic Republic of Congo) and Sudan. 1959–1962	First isolation of ONNV and A. funestus identified as a vector. More than 2 million infections reported during the 3-year span.	[14]
Kenya, 1969	Serological survey identified 782 positive patients with ONNV antibodies, with a 35% infection rate in children below 6 years-old (therefore unrelated to the 1959 outbreak).	[16]
Ghana, Sierra Leone and Nigeria, 1974–75	3 confirmed imported cases in Canada revealed sporadic transmission in Ghana, Sierra Leone and Nigeria.	[17]
Ivory Coast, 1984–85	33 infections reported, mosquito isolates identified both A funestus and A gambiae as carriers of ONNV.	[18]
Rakai district, south Uganda, 1996–97	121 infections reported.	[19]
Nicla Border Camp, western Ivory Coast, 2003	8 confirmed cases, 31 were ill with similar symptoms. Total cases unknown in a population of 8000.	[20]
The Sarh region, southern Chad, 2004	Singular case of infection in a 19-year-old French soldier returning from a mission in the city of Sarh, Chad.	[21]
Coastal Kenya, 2009–2010	418 serologically positive samples for ONNV of 443 screened samples. Total cases unknown.	[22]
Mali, 2016	Serological study indicating endemic circulation in Mali.	[23]
Kenya, 2016–2017	Screening of febrile patients showed recent circulation of CHIKV and ONNV in Taita-Taveta County and Nairobi	[24]

Figure 3. Overview of ONNV. (a) TEM images of purified ONNV particles taken at 2 different magnifications (courtesy of Malleret, B. and Lee, E.Q.H.). (b) Schematic of the ONNV genome, which consists of a single-stranded positive sense RNA with 2 reading frames, the first encodes nsP1–4, this is followed by a sub genomic sequence that encodes for the viral structural proteins (Capsid, envelope 1–3 and membrane associated 6K protein). (c) Diagram describing the replication cycle of ONNV. Once ONNV releases its genetic material in the host cell, the nsP1–4 proteins are translated, nsP2 then proceeds to cleave the viral polymerase nsP4 which goes on to generate complementary negative RNA strands for rapid viral RNA replication. nsP2 then later cleaves both nsP1 and nsP3 to form the late viral replicase machinery needed for structural protein synthesis and virion assembly utilising host post-translational modifications via ER-golgi apparatus.

Figure 4. Clinical manifestation of ONNV infection. Diagram showing the general disease progression of ONNV. After being bitten, the virus typically takes ~8 days before the patient becomes symptomatic. This progresses to the acute phase (days 8–15) with generalised symptoms such as fever, rashes, and headaches. In rare cases, ONNV infections will cause lymphoedema and retro-orbital pain, joint pain might also begin to manifest during this time. If not self-limiting, the disease will progress to enhanced pain and inflammation in the joints (targeting extremities) which in rare cases can last for several months (chronic phase).

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Data availability statement

Data sharing is not applicable to this article as no new data were created or analysed in this study.