Influenza

Influenza is the most common virus of the Orthomyxoviridae family.

Influenza A

An enveloped virus with negative sense, single-stranded segmented RNA. Found in wild aquatic birds.

Hemagglutinin (HA): Surface protein that binds virus to host cells. Determines the virus specificity (tissues to infect).
Neuraminidase (NA): Surface protein that cleaves progeny into single virion particles. This is important as only single viruses are virulent.

The HA/NA combo determines the strain, e.g., H1N1.

Replication

vRNP (viral ribonuclear protein complex) is bound to the segmented RNA and its RNA polymerase.

1. Viral Hemagglutinin triggers endocytosis
2. Replication inside the nucleus. Unique to influenza as RNA viruses usually do so in the cytoplasm.
3. New viruses buds out from the host cell and are cleaved into single virus particles by neuraminidase.

Diagnosis

Can be difficult to diagnose based on signs and symptoms alone as other infections share similar symptoms.

Rapid Influenza diagnostic test (nose swab): Fast and easy antigen detection.
RT-PCR: Determines subtypes. Only in severe cases.

Clinical features

Rapid onset of upper respiratory tract symptoms (e.g. fever, chills, myalgia, headaches, malaise, non-productive cough, sore throat, rhinitis).

Incubation period: 1 to 4 days
Infectiousness (viral shedding): 3-7 days

Uncomplicated Influenza resolves after 3-7 days. Although cough and malaise can persist for longer. Complicated Influenza has an increased morbidity and mortality for at-risk populations.

Treatment

Neuraminidase antagonist

By blocking neuraminidase activity, progeny viruses are clumped together instead.

Oseltamivir (oral), Zanamivir (inhaler), or Peramivir (IV).

Matrix protein antagonist

The M2 protein is involved with releasing the RNA into the cytoplasm. By blocking the matrix protein, the virus is not able to replicate. Only helpful within two-days of infection.

Amantadine (oral), Rimantadine.

RNA polymerase antagonist

Directly blocks replication.

Baloxavir marboxil (oral).

Seasonal Vaccines

Inactivated Vaccine: Grown in chicken embryonated eggs. Most popular approach. Includes Influenza A and B strains that WHO predicts to be the circulating seasonal influenza.

Live Attenuated Vaccine: Grown in chicken eggs. A real virus modified to only survive and replicate in the upper respiratory tract, but can’t replicate in the lower respiratory tract. It cannot be given to young children under 2 years old, pregnant women, and the immunocompromised.

Recombinant Hemagglutinin Vaccine: Fast production. Does not produce as strong of an immunogenicity response as the inactivated/live vaccines, but is beneficial to control a mid-season outbreak of a new HA strain.

Epidemiology

Spill-over events

When viruses cross into new species. For example, H5N1 can hop from birds to humans but it doesn’t transmit between humans. Cause very patients to be very ill.

Host properties

The strength of the hosts immune defense, susceptibility of host cells for invasion, and the right receptor profile determines the infectivity.

Sialic acid alpha-2,6 receptors: Found on humans, so a virus needs to have the right hemagglutinin that can bind.
Sialic acid alpha-2,3 receptors: Specific to birds. However, pigs have both human and avian receptors, which makes pigs a good intermediate for the influenza to jump between avian and human species.

Antigenic drift

Point mutations are made in the HA and NA genes, making the proteins unrecognizable to formerly infected hosts. This is the reason we need new flu vaccines every year.

Antigenic shift (reassortment)

Multiple strains infect a host at the same time and combine genetic material to create one new virus. This is the cause of many modern pandemics.