Negative Sense RNA Viruses: Rhabdoviruses, Filoviruses, Bunyaviruses and Arenaviruses

Rabies virus

Genome: negative-sense ssRNA. Envelope: present, with a characteristic bullet-shaped virion morphology, a distinctive structural feature among the negative-sense RNA viruses.

Transmission is by bite or, less commonly, scratch or mucous membrane contact with infected saliva from an infected mammal. Wild animal reservoirs vary by region and include bats, raccoons, foxes, and skunks. Dogs remain the dominant global source of human exposure and death, particularly where canine vaccination programmes are ineffective.

Tropism is peripheral nerve tissue. The defining feature is slow retrograde axonal transport along peripheral nerves toward the central nervous system.

This transport underlies the variable, sometimes prolonged incubation period, ranging from days to, rarely, years. It generally correlates inversely with the distance of the bite site from the central nervous system.

The slow transport creates the window in which post-exposure prophylaxis, rabies immunoglobulin plus vaccine, remains effective. Prophylaxis given before the virus reaches the central nervous system can still prevent disease. Established central nervous system infection is uniformly fatal, with only exceedingly rare exceptions.

Rabies encephalitis presents after the incubation period with a prodrome of fever, malaise, and paraesthesia or pain at the bite site. This reflects local viral replication and nerve involvement before overt neurological symptoms. Acute neurological illness then follows in one of two recognised clinical patterns.

Furious rabies produces agitation, hyperactivity, and hydrophobia. This is the classically described and historically defining presentation, and hydrophobia reflects painful pharyngeal spasm triggered by attempts to swallow.

Paralytic rabies produces an ascending flaccid paralysis. It is less often recognised and more easily misdiagnosed, given its resemblance to other causes of acute flaccid paralysis. Once symptomatic, the disease is almost uniformly fatal.

Diagnosis is predominantly clinical and epidemiological: bite history, animal species, and local rabies prevalence. Decisions on post-exposure prophylaxis are time-critical and should not be delayed pending laboratory confirmation.

Direct fluorescent antibody testing of brain tissue remains the diagnostic reference standard. The tissue comes from the biting animal where available or, in fatal human cases, post-mortem.

Negri bodies, eosinophilic cytoplasmic inclusions in infected neurons, classically in the hippocampus, are a classic though not universally sensitive histopathological finding.

Ebola virus and Marburg virus

Genome: negative-sense ssRNA. Envelope: present, with a characteristic elongated, filamentous virion morphology. The family name reflects this thread-like, "filo," structure.

Transmission is by direct contact with infected body fluids from a symptomatic patient: blood, vomitus, diarrhoeal stool, and other secretions. The initial spillover event comes from an infected animal. Bats are the suspected natural reservoir for both viruses, with nonhuman primates implicated as an intermediate amplifying host in some outbreaks.

Transmission generally requires direct contact with infected fluids from a symptomatic individual. It does not generally occur during the asymptomatic incubation period.

This matters for outbreak containment. The strategy is contact tracing and symptom monitoring of exposed contacts, not presumptive indefinite isolation of all exposed but asymptomatic individuals.

Tropism is broad, including monocytes and macrophages, dendritic cells, hepatocytes, and vascular endothelium. The endothelial tropism directly contributes to the vascular permeability and haemorrhagic manifestations of severe disease.

Disease is severe viral haemorrhagic fever. Abrupt febrile onset is followed, in the more severe presentations, by gastrointestinal symptoms, widespread haemorrhagic manifestations, and multiorgan failure. Case fatality rates are substantial, vary by virus species and outbreak, and are among the highest of any human viral infection.

Diagnosis relies on PCR as the standard confirmatory test. It is performed under strict biosafety precautions given the organism's severity and transmissibility via direct contact.

Infection prevention requires specific personal protective equipment and safe burial practice, given the recognised risk of transmission from the bodies of deceased patients.

This is a broad, taxonomically diverse order, recently reorganised at a higher taxonomic level in formal virus classification. It is still commonly grouped clinically as "bunyaviruses" for teaching purposes.

It encompasses several medically important, generally arthropod-borne or rodent-associated viruses. They share a segmented, negative-sense RNA genome, which is ambisense in some members, a further genome organisation variant.

Hantavirus is transmitted by inhalation of aerosolised rodent excreta: urine, faeces, saliva. It does not use an arthropod vector, which distinguishes its transmission route from most other members of this group.

It causes two principal clinical syndromes, depending on the hantavirus species and geographic distribution.

• Haemorrhagic fever with renal syndrome occurs predominantly with Old World hantavirus species. It features fever, haemorrhagic manifestations, and acute kidney injury.
• Hantavirus pulmonary syndrome occurs predominantly with New World, particularly North and South American, hantavirus species. It features rapidly progressive, often severe noncardiogenic pulmonary oedema and respiratory failure.

Rift Valley fever virus is transmitted by mosquito bite and by direct contact with infected livestock blood and tissue.

The virus is maintained primarily in livestock, particularly sheep and cattle. Contact is a recognised occupational risk for herders, farmers, and abattoir workers. Epizootic outbreaks in animals often precede and predict human outbreak risk.

It causes a spectrum from a mild, self-limited febrile illness, the most common outcome, to more severe disease in a minority of cases. Severe disease includes haemorrhagic fever, encephalitis, or ocular disease (retinitis).

Crimean-Congo haemorrhagic fever virus is transmitted by tick bite (specifically Hyalomma ticks) and by direct contact with infected animal or human blood and tissue.

Alongside the filoviruses, it is one of the few viral haemorrhagic fever agents with a well-recognised risk of healthcare-associated and nosocomial transmission from an infected patient to carers.

It causes a severe haemorrhagic fever with a substantial case fatality rate. Its distribution across parts of Africa, the Balkans, the Middle East, and Asia corresponds to the geographic range of the vector tick.

Lassa fever virus

Genome: ambisense ssRNA. Parts of the genome are negative-sense and parts positive-sense within the same RNA segment, a structural variant distinct from the purely negative-sense pattern of most other viruses in this group. Envelope: present.

Transmission is by contact with excreta (urine, faeces) from infected rodents, via contaminated food, dust, or direct contact. The multimammate rat is the principal reservoir in West Africa, where the virus is endemic.

Person-to-person transmission also occurs, particularly in healthcare settings, via contact with infected body fluids, similar in general principle to filovirus transmission.

Tropism is broad, including the reticuloendothelial system. In severe disease, involvement contributes to vascular and multiorgan dysfunction.

Disease spans a spectrum. Asymptomatic or mild febrile illness is the outcome in the substantial majority of infections, a contrast to the filoviruses, which more consistently produce severe, clinically apparent disease.

Severe disease features haemorrhagic manifestations and multiorgan involvement.

A classically tested complication is sensorineural hearing loss. It can occur even after apparently mild acute illness and is the most common long-term sequela of Lassa fever infection.

Diagnosis relies on PCR, the standard acute-phase test, and serology. Biosafety precautions are similar to those for the filoviruses, given the organism's severity potential and person-to-person transmissibility.