Pathogen Profiles: Measles Virus

Measles virus (MeV) is making a comeback globally, with declining immunization coverage driving emerging outbreaks.

Measles infection is typified by initial cold-like symptoms (a fever and sore throat), followed by a cough, runny nose, lack of appetite and energy, a blotchy red rash, and “Koplik’s spots”. A great proportion of these symptoms relate to the manifestations of the general host immune response to viral infections; the immune system approaches full gear (using our energy), alarm cytokines are released by immune cells that have been engaged with viral antigen (contributing to fever), and increased/thickened mucous production occurs (contributing to the runny nose).

The observation of a blotchy red rash can help confirm MeV as the causative agent of a given illness; this red rash is observed to start at the face and spread down the body, a progression that is characteristic of MeV and distinct from rashes caused by other viruses (which typically start at the torso). Koplik’s spots are slightly-raised bluish-white spots found on the buccal mucosa of those infected with MeV (as a result of glandular epithelial cells having been destroyed), typically about a day before the emergence of the rash characteristic of MeV. The observance of Koplik’s spots are useful not only in the context of active diagnosis (with these spots on the mucosa being characteristic of MeV specifically), but also in the context of timely diagnosis (Koplik’s spots are a part of measles’ pre-eruptive stage, which occurs before the point of peak infectiousness, meaning that the timely observation of these spots can lead to preemptive measures being taken that limit MeV’s spread throughout the community).

Measles virus utilizes a myriad of mechanisms to promote infection and spread throughout the host. Its portal of entry is the respiratory tract; a highly contagious virus, measles is transmissible via nasal and throat secretions, and most commonly enters the respiratory tract as small aerosols In the respiratory tract, it can infect the apical side of epithelial cells, ultimately infecting resident dendritic cells and alveolar macrophages that are reaching out into the airway lumen. This is usually followed by systemic dissemination of the virus, with infected dendritic cells and macrophages traveling to local lymph nodes, where other immune cells become infected. Immune cells travel to the skin, infecting skin lymphoid cells and keratinocytes, with a similar phenomenon occurring at hair follicles and sebaceous glands (which result in the virus’ further spread). Viral replication occurs at these skin surfaces, immune responses are subsequently initiated, blood vessels expand, and CD8 T cells are recruited to kill any infected cells of the skin, with the associated swelling and tissue damage causing the rash characteristic of MeV infection. Eventually, infected lymphoid cells return to the underlying respiratory tissue, where they release virions. The resulting basolateral infection of the respiratory epithelia allows virions to travel back into the respiratory lumen, from where they may be expelled (via respiratory transmission) to potentially infect other susceptible and permissive hosts

Given how contagious that measles is, for those who lack protection, the virus poses a significant risk. In lacking vaccine-induced immunity against measles, one lacks any sort of immunological memory or preparedness (such as memory B/T cells, or circulating neutralizing antibodies) to clear and/or minimize the extent of infection in the event of exposure to measles. Apart from being at risk of developing some or all of the symptoms that are characteristic of general viral infections (such as cold-like symptoms), one is at risk of developing other complications related to MeV infections. These include blindness and encephalomyelitis (as part of systemic spread, infected lymphocytes can squeeze through the blood brain barrier and promote infection in regions of the brain), pneumonia (as a result of infection weakening the lungs, thereby increasing susceptibility to opportunistic pathogens), or other respiratory infections.

Protection against measles can be conferred through administration of the MMR vaccine, which also protects against two other pathogens: mumps and rubella. A childhood vaccine, it is typically administered as a series of two separate doses – one at 12 months of age, and the other between the ages of 4 and 6 (in Vancouver, BC, Canada).

For those who have yet to be immunized (like older children or even adults), it is encouraged to receive both doses of the MMR vaccine.

A live attenuated vaccine, antigens associated with the MMR vaccine components engage pathogen recognition receptors (PRRs) and are taken up and presented by antigen presenting cells, resulting in the activation of CD4 T-cells, CD8 T-cells, and B cells respectively. Antibodies are produced, as are memory T and B-cells (the latter of which is now capable of secreting class-switched, high-affinity antibodies against measles).

Since the MMR vaccine is a live-attenuated vaccine, there is a risk of it reverting to a virulent form (thereby replicating in the host, producing detectable levels of viral RNA and protein, and engaging the host immune system with the antigens it contains) – such a phenomenon can explain incidences of infection or positive lab results subsequent to administration of the MMR vaccine. Along those lines, live attenuated vaccines are not recommended for those who are immunocompromised and possess weakened or developing immune systems (like infants).

Nevertheless, vaccines save lives, and now more than ever, it is required to curb the trajectory of a pathogen that was once thought to be nearly ‘eliminated’.

References:

1. https://www.ncbi.nlm.nih.gov/books/NBK557716/

2. https://www.cdc.gov/measles/signs-symptoms/index.html

3. https://pmc.ncbi.nlm.nih.gov/articles/PMC7149578/

4. https://pubmed.ncbi.nlm.nih.gov/30833942/

5. https://pmc.ncbi.nlm.nih.gov/articles/PMC4997572/

6. https://pubmed.ncbi.nlm.nih.gov/36293745/

7. https://pmc.ncbi.nlm.nih.gov/articles/PMC8263189/

8. https://pubmed.ncbi.nlm.nih.gov/36560645/

9. https://pubmed.ncbi.nlm.nih.gov/32891958/

10. https://pmc.ncbi.nlm.nih.gov/articles/PMC5086614/

11. https://pubmed.ncbi.nlm.nih.gov/33502929/