News Excerpt:
Scientists at the Institute of Molecular Virology at the Ulm University Medical Centre, Germany, have identified a novel defence mechanism the human body uses to prevent Zika and some other viruses from transmitting via non-conventional routes.
Background:
- The mere presence of a virus in a bodily fluid doesn’t mean it is transmitted via that route.
- The Zika, dengue, and chikungunya viruses are present in fluids like saliva and semen but don’t spread orally or sexually.
- This fact has puzzled scientists for years; now, a research team has finally explained why.
What does a virus do inside the body?
- Transmission is a crucial event in a virus’s life cycle. A virus that can’t transmit is of no consequence to anyone.
- Most human viruses achieve this by ensuring they are present in bodily fluids that contact the outer environment and, subsequently, a new host.
- Once inside the new host, a virus must be present at the correct location to infect new target cells.
- Viruses are usually highly selective in the cells they infect. This phenomenon, called tropism, occurs because most viruses have special proteins on their outer surface that make contact with a receptor on the host cell.
- Any cell-type that makes the receptor can be infected by the virus.
- For example, the receptor for HIV is a protein called CD4. Only cells that make the CD4 protein, such as T-cells and macrophages, can be infected by HIV.
- Similarly, SARS-CoV-2 uses a receptor called ACE2. Cells of the respiratory tract and some cardiovascular cells all express ACE2 and are target cells for SARS-CoV-2.
- HIV can’t infect respiratory cells, and SARS-CoV-2 can’t infect T-cells or macrophages.
- Viral transmission is an outcome of a chase inside the host: between the virus making copies of itself and the immune system trying to destroy the virus and infected cells.
- The virus must transmit before the immune system beats it or the host dies.
- Viruses use this strategy to achieve this by making proteins on the surface that have receptors on multiple cell-types.
- Such a strategy will allow them to infect different cell types, allowing them access to multiple body fluids and enabling faster transmission.
What is the PS receptor?
|
Key highlights of the study:
- The study, published in the journal Nature Microbiology, explains how the body uses extracellular vesicles in these bodily fluids to inhibit viral infection.
- Vesicles are small structures enclosed by fat that a cell uses to transport substances from one part of the cell to another.
- When they are secreted outside the cell, they’re called extracellular vesicles.
- The researchers discovered these extracellular vesicles are abundant in saliva and semen and contain the same PS proteins on their surface that viruses like Zika use for infection.
- The team also discovered the concentration of these extracellular vesicles that contain PS is low in blood and high in saliva and semen.
- Through a series of experiments, they demonstrated the PS-containing vesicles compete for the same receptors the viruses use for entry, thus crowding the latter out and preventing infection.
- The group also showed that all viruses that use the PS receptor for apoptotic mimicry – the dengue, chikungunya, West Nile, ebola, and the vesicular stomatitis viruses – are inhibited by the presence of extracellular vesicles.
- The presence of vesicles didn’t affect the infectivity of viruses that don’t use the PS receptor for entry, such as HIV and SARS-CoV-2.
Significance of the discovery:
- The discovery of PS-coated vesicles for immunity represents a novel type of host defence against viral infection.
- While it is too early to speculate on potential therapeutic applications from this discovery, it opens up avenues for further research.
- One thought-provoking notion arising from the study is the possibility that PS-containing vesicles in humans could have influenced the evolution of mosquito-borne viruses.