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.

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.