Orthomyxo and Paramyxoviruses — Influenza Drift and Shift, Measles and Mumps Virology

Both families are enveloped, negative-sense, single-stranded RNA viruses that infect the respiratory tract and are spread by respiratory droplets. The key microbiology difference that exams test is the influenza genome is segmented (eight RNA segments in influenza A and B), which allows reassortment, whereas paramyxoviruses such as measles and mumps have non-segmented negative-sense RNA genomes.

There are four types of influenza virus: A, B, C and D. Types A and B cause human epidemics each season. All are enveloped, negative-sense, single-stranded RNA viruses; influenza A and B contain eight RNA segments encoding the polymerase subunits (PB2, PB1, PA), the surface glycoproteins haemagglutinin (HA) and neuraminidase (NA), the nucleoprotein (NP), matrix protein M1, membrane protein M2, and the non-structural proteins NS1 and nuclear export protein (NEP).

• Influenza A is subtyped by HA and NA, for example H1N1 and H3N2; there are 18 HA and 11 NA subtypes.
• Influenza B is not subtyped; it is divided into B/Yamagata and B/Victoria lineages.
• Only influenza A has caused pandemics; wild aquatic birds are its natural reservoir, and pigs, horses and poultry are also infected.
• The current human seasonal subtypes are A(H1N1)pdm09 and A(H3N2), plus the two B lineages.

Influenza evades immunity in two ways. Antigenic drift is the gradual accumulation of mutations in HA and NA, which lets the virus escape antibodies from previous infection or vaccination; it is why vaccines must be updated frequently. Antigenic shift is a drastic change in the HA (and sometimes NA) of influenza A viruses, usually because a human strain acquires HA or NA from an animal strain by reassortment; shift is associated with pandemics.

• In 1957 an H2N2 virus replaced H1N1; in 1968 H3N2 emerged; H1N1 reappeared in 1977 and co-circulated with H3N2.
• The 2009 pandemic was caused by a novel H1N1 reassortant previously circulating in pigs; since 2009, H3N2, pandemic-derived H1N1 and two B lineages co-circulate.
• Avian viruses such as H5N1, H7N9 and H5N8 infect humans occasionally but have not shown sustained human-to-human transmission; they would need further adaptation.
• Because HA is the main component of inactivated vaccines, surveillance programmes track antigenic change, and WHO recommends vaccine composition twice a year for the northern and southern hemispheres.

Influenza is an acute respiratory illness with abrupt fever, cough, sore throat, myalgia, headache and coryza. The incubation period is about 2 days (range 1 to 4 days); patients can transmit before symptoms appear and until 5 to 7 days after infection. Illness lasts 7 to 10 days and is self-limited in healthy people, but high-risk groups — young children, the elderly, pregnant women, the immunocompromised and those with chronic lung or heart disease — can develop primary viral pneumonia, secondary bacterial pneumonia and death. WHO estimates that seasonal influenza causes 290,000 to 650,000 respiratory deaths each year.

Measles (rubeola) is caused by the measles virus, an enveloped, single-stranded, negative-sense RNA virus of the genus Morbillivirus in the family Paramyxoviridae. Its genome encodes six structural proteins (nucleoprotein, phosphoprotein, matrix, fusion, haemagglutinin and large protein) and two non-structural proteins, V and C. The haemagglutinin attaches the virus to the host cell. Humans are the only reservoir.

• WHO case definition: any person with fever, generalised maculopapular rash, and cough, coryza or conjunctivitis.
• Diagnosis: RT-PCR on throat, nasopharyngeal, blood or urine samples (most sensitive in the first 3 days of rash) is the most common laboratory test; measles-specific IgM confirms the diagnosis but may be falsely negative in up to 25% when tested within 3 days of rash onset. The gold-standard serology is the plaque reduction neutralisation assay.
• Treatment: no specific antiviral; supportive care, isolation and vitamin A. WHO advises two doses of vitamin A (immediately and the next day) for all suspected cases in children under 5, and a third dose 4–6 weeks later if eye signs of deficiency are present.
• Vaccine: two doses are recommended; WHO advises the first dose at 9 months where measles is common and at 12–15 months elsewhere, and the second dose in later childhood (usually 15–18 months). Two doses give about 97% protection.
• To prevent outbreaks about 95% of the population must be immune.

Mumps is caused by a Rubulavirus of the Paramyxoviridae family, an enveloped, single-stranded RNA virus. Its surface haemagglutinin-neuraminidase (HN) proteins bind sialic acid on host cells to enable entry and are the main target of neutralising antibodies. There are 12 genotypes; the MMR vaccine strain used in the United States (Jeryl Lynn, genotype A) protects against all of them. Humans are the only natural host. Mumps is the only known cause of epidemic parotitis and the most common cause of infectious parotitis.

• Treatment is supportive: analgesia, compresses; for orchitis scrotal elevation and cold compression. Glucocorticoids have no proven benefit in mumps orchitis.
• Droplet precautions and isolation for 5 days after onset of parotid swelling.
• Differential of parotitis: other viruses (EBV, influenza A, parainfluenza 1 and 3, adenovirus, enteroviruses, HIV), suppurative bacterial parotitis, sialolithiasis, Sjögren syndrome and tumours.
• Prevention: two doses of MMR; outbreaks have occurred even among vaccinated young adults, which has raised concern about waning immunity and incomplete two-dose coverage.

• Genome — influenza A and B have 8 segments (segmented, negative-sense RNA); measles and mumps are non-segmented paramyxoviruses.
• Shift vs drift — reassortment vs point mutation; which causes pandemics (shift, influenza A only).
• HA vs NA functions and which antiviral targets which (NA inhibitors, M2 inhibitors).
• Amantadine active only against influenza A.
• Measles — genus Morbillivirus, Koplik spots, 3 Cs, rash direction, vitamin A, SSPE, immune amnesia.
• Mumps — Rubulavirus, parotitis, orchitis, aseptic meningitis, only epidemic parotitis cause.
• Vaccines — annual influenza vaccine; MMR live attenuated; first measles dose at 9 months where measles is common.