A 41-year-old woman comes to the emergency department due to 2 days of severe shortness of breath, high fevers, cough, and myalgias. The patient is a businesswoman who works in the poultry industry. She recently returned from a trip to China, where she visited several factories in different parts of the country. Her temperature is 39.1 C (102.4 F). The patient is in respiratory distress, and crackles and diffuse wheezes are present on pulmonary examination. Laboratory results show that she contracted an orthomyxovirus that was responsible for an upper respiratory infection epidemic in China. Transmission of the virus was originally thought to occur only through contact with poultry, but during the outbreak, sustained human-to-human transmission was observed. Which of the following is most likely responsible for the infectivity of this virus in humans?

Question

A 41-year-old woman comes to the emergency department due to 2 days of severe shortness of breath, high fevers, cough, and myalgias.  The patient is a businesswoman who works in the poultry industry.  She recently returned from a trip to China, where she visited several factories in different parts of the country.  Her temperature is 39.1 C (102.4 F).  The patient is in respiratory distress, and crackles and diffuse wheezes are present on pulmonary examination.  Laboratory results show that she contracted an orthomyxovirus that was responsible for an upper respiratory infection epidemic in China.  Transmission of the virus was originally thought to occur only through contact with poultry, but during the outbreak, sustained human-to-human transmission was observed.  Which of the following is most likely responsible for the infectivity of this virus in humans?

Quizplus · Accepted Answer

11ec160b_3879_f2b7_9249_23a57aa9315b_MD0001_00 Influenza viruses (orthomyxoviruses) are respiratory pathogens that can affect several species, including humans, birds, and swine. They possess the surface proteins hemagglutinin (HA) and neuraminidase (NA), which are virulence factors required for infectivity. These proteins are also targets of the immune system, and neutralizing antibodies against them can confer immunity to specific influenza strains. As such, HA and NA are under constant selective pressure both to maintain species-specific virulence and evade immune recognition. Orthomyxoviruses contain a segmented genome, and HA and NA are coded by separate RNA segments. This allows for genetic reassortment when 2 distinct strains infect the same cell. For instance, avian coinfection with a human influenza A virus (which can also infect birds, the reservoir species for all influenza A subtypes) and an animal influenza A virus can lead to the human-type HA and the animal-type NA being packaged together into the same virion. This has the potential to create a novel strain of virus to which humans are susceptible but have no immunologic resistance. This phenomenon is known as antigenic shift, and is responsible for the majority of pandemics and epidemics of influenza A. (Choice A) Antigenic drift refers to point mutations in HA and NA genes that slightly alter the product proteins, allowing them to evade immune recognition and possibly increasing infectivity of the virus. However, a change in species-to-species transmission likely represents a major modification in protein structure that is better explained by RNA segment reassortment. (Choice B) In genetics, complementation occurs when 2 different strains of a mutant organism are able to produce wild-type offspring. Typically, both parents have homozygous mutations in different genes within the same metabolic pathway. When they are crossed, the offspring inherits 1 normal allele from each parent, allowing them to bypass both of the metabolic blockades and display the wild-type phenotype. (Choice C) Frameshift mutations result when a number of bases that are not a multiple of 3 are added to or deleted from the coding region of a gene. This typically results in premature termination of translation and a truncated protein containing the wrong amino acids. (Choice E) Phenotypic mixing occurs when 2 viruses infect the same cell and progeny viruses exhibit coat or envelope proteins not coded for by the genetic material packaged within them. However, subsequent progeny express only the proteins encoded by their genome. The above scenario is not an example of phenotypic mixing as human-to-human transmission was sustained. Educational objective: Influenza epidemics and pandemics are typically caused by reassortment of the RNA segments coding for hemagglutinin or neuraminidase proteins (major antigenic shifts). This process can occur between human and animal strains of influenza A virus in avian or swine hosts.

A 41-Year-Old Woman Comes to the Emergency Department Due to 2