Positive Sense RNA Viruses: Flaviviruses, Togaviruses and Coronaviruses

Flaviviruses are enveloped, positive-sense RNA viruses. The majority of medically important members are transmitted by arthropod vectors, predominantly mosquitoes.

Dengue virus

Genome: positive-sense ssRNA. Envelope: present. Transmission is by Aedes mosquito bite, predominantly Aedes aegypti. Tropism is broad, including monocytes and macrophages and endothelial cells, the latter tropism directly relevant to the vascular leak pathophysiology of severe disease.

Classic dengue fever presents with high fever, severe myalgia and arthralgia, sometimes called breakbone fever, retro-orbital headache, and a characteristic rash. Severe dengue, previously termed dengue haemorrhagic fever or dengue shock syndrome, involves plasma leakage, thrombocytopenia, and haemorrhagic manifestations.

A critical and distinctive epidemiological feature is that severe disease risk is substantially higher on secondary infection with a different dengue serotype than on primary infection. This reflects antibody-dependent enhancement, in which non-neutralising antibody from the prior, different-serotype infection paradoxically facilitates viral entry into Fc-receptor-bearing cells during the second infection.

Diagnosis relies on NS1 antigen testing, useful early in illness, PCR, and serology, IgM and IgG.

Yellow fever virus

Genome: positive-sense ssRNA. Envelope: present. Transmission is by Aedes mosquito bite, maintained in both a sylvatic, jungle, nonhuman primate reservoir and an urban, human-to-human via mosquito, transmission cycle. Tropism is hepatocytes, directly explaining the disease's hepatic manifestations, along with kidney and other organs in severe disease.

Disease ranges from mild febrile illness to severe disease featuring jaundice (the origin of the name), haemorrhage, and multiorgan failure.

The clinical course is classically biphasic: an initial febrile phase, a brief apparent improvement, then, in a smaller proportion of patients, progression to a severe toxic phase.

Diagnosis relies on serology and PCR. A highly effective live-attenuated vaccine is available and is specifically required for travel to and from many endemic countries under International Health Regulations.

West Nile virus

Genome: positive-sense ssRNA. Envelope: present. Transmission is by Culex mosquito bite, maintained in a bird reservoir with humans as incidental, dead-end hosts not contributing meaningfully to onward transmission. Tropism is broad, with specific neurotropism relevant to its most severe presentation.

The great majority of infections are asymptomatic or produce a mild febrile illness. A small minority, particularly in older or immunocompromised patients, develop neuroinvasive disease: meningitis, encephalitis, or a distinctive acute flaccid paralysis resembling poliomyelitis, reflecting anterior horn motor neuron involvement, an important overlap in clinical pattern with poliovirus despite the two organisms being entirely unrelated taxonomically.

Diagnosis relies predominantly on serology, IgM, including cerebrospinal fluid IgM for neuroinvasive disease, since viraemia is often brief and may have resolved by the time of clinical presentation, limiting PCR sensitivity for this specific organism.

Zika virus

Genome: positive-sense ssRNA. Envelope: present. Transmission is by Aedes mosquito bite, and, distinctively among the arboviruses, also sexually and transplacentally, both routes of major clinical significance. Tropism is broad, with a specific and defining tropism for neural progenitor cells during fetal development.

The infected adult is typically mildly or asymptomatically affected: low-grade fever, rash, conjunctivitis, arthralgia. The major clinical significance of this virus lies in congenital Zika syndrome following maternal infection during pregnancy, causing microcephaly and a range of other severe neurological and ocular abnormalities, reflecting the neural progenitor cell tropism above. Zika infection is also associated with an increased risk of Guillain-Barre syndrome.

Diagnosis relies on PCR, blood and urine, given a comparatively longer window of detectable viruria than viraemia for this specific organism, and serology, with specific caution required given serological cross-reactivity with other flaviviruses, notably dengue, complicating interpretation in patients with possible exposure to both.

Chikungunya virus

Genome: positive-sense ssRNA. Envelope: present. Transmission is by Aedes mosquito bite. Tropism is joint and musculoskeletal tissue, directly underlying its defining clinical feature.

Disease presents as an acute febrile illness with severe, often markedly debilitating polyarthralgia and polyarthritis, from which the name derives, a term from the Makonde language meaning "that which bends up," describing the stooped posture of affected patients. In a meaningful proportion of patients this can persist as chronic arthralgia for months to years after the acute illness has otherwise resolved.

Diagnosis relies on PCR early in illness and serology, IgM and IgG.

Rubella virus

Genome: positive-sense ssRNA. Envelope: present. Transmission is by respiratory droplets, a notable contrast with chikungunya, both togaviruses but with entirely different transmission routes, chikungunya vector-borne and rubella purely respiratory. Tropism is respiratory epithelium initially, with subsequent viraemic dissemination, including, critically, transplacental spread when maternal infection occurs during pregnancy.

In postnatally acquired infection, disease is typically mild, with a diffuse maculopapular rash, classically less confluent and shorter-lived than measles, generalised lymphadenopathy, particularly postauricular and suboccipital, a useful distinguishing clinical feature, and, in adult women specifically, a notable tendency toward transient arthralgia and arthritis.

The major clinical significance of this virus lies in congenital rubella syndrome following maternal infection during pregnancy, with risk and severity highest with infection in the first trimester. This produces the classic triad of sensorineural deafness, cardiac defects, classically patent ductus arteriosus, and cataracts, alongside a range of other possible abnormalities.

Diagnosis relies on serology, IgM for recent or acute infection, IgG for immunity status, routinely checked antenatally in many settings specifically to identify susceptible pregnant women.

Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses with an unusually large genome for an RNA virus.

Large, characteristic club-shaped surface glycoprotein spikes project from the envelope. Their spike-studded appearance resembles a solar corona under electron microscopy, which gives the family its name. The spikes directly mediate receptor attachment and are the antigenic target of neutralising antibody and vaccine design.

Respiratory tropism is dominant across the family, targeting respiratory epithelium via specific receptor interactions that vary by individual coronavirus species, for example the well-characterised use of the ACE2 receptor by SARS-CoV-2 and the original SARS-CoV. Some coronaviruses are also capable of enteric tropism and gastrointestinal manifestation in a subset of infections.

Several endemic human coronavirus species, including strains designated 229E, NL63, OC43, and HKU1, circulate widely and are collectively responsible for a meaningful minority of common cold presentations, generally causing mild, self-limited upper respiratory illness.

SARS-CoV is the cause of severe acute respiratory syndrome, which emerged in 2002 to 2003. It was a zoonotic spillover event with a bat reservoir and civet cats implicated as an intermediate host in the original outbreak.

It produced severe pneumonia with high mortality. It was contained relatively successfully through aggressive public health measures before achieving sustained global spread.

MERS-CoV is the cause of Middle East respiratory syndrome, a further zoonotic coronavirus. It has a bat reservoir, and dromedary camels are the recognised intermediate and ongoing reservoir for human exposure.

It produces severe pneumonia with a high case fatality rate. It remains geographically concentrated predominantly in the Arabian Peninsula, with periodic exported cases elsewhere.

SARS-CoV-2 is the cause of COVID-19, which emerged in late 2019 and achieved sustained global pandemic spread.

The clinical spectrum ranges from asymptomatic infection through mild upper respiratory illness to severe pneumonia and acute respiratory distress syndrome. A wide range of extrapulmonary and post-acute manifestations is recognised.

Rapid vaccine development, using novel mRNA vaccine technology among other platforms, was a landmark achievement in modern virology and vaccinology.

Diagnosis across this family relies predominantly on PCR from a respiratory specimen, nasopharyngeal swab being standard. Rapid antigen testing offers faster, lower-sensitivity point-of-care detection, particularly widely deployed for SARS-CoV-2. Serology is used predominantly for retrospective and epidemiological assessment of past infection rather than acute diagnosis.