New Discovery! How Extracellular Vesicles Defend Against Zika and Dengue Transmission? – Top 10 Facts

Introduction about Extracellular Vesicles UPSC

Welcome to PreCrack! Recently, in a research, scientists have identified a novel defence mechanism. Our human Body uses this defence mechanism to prevent some viruses from transmitting via non-conventional routes. This Defence Mechanism works with Extracellular Vesicles in human body.

Why is Extracellular Vesicles in the News? – UPSC Current Affairs

Extracellular vesicles are making headlines in the news because scientists have found a new defence mechanism in Human Body. These Extracellular Vesicles plays a crucial role in defending our bodies against viruses. These tiny structures have a special power: they can stop viruses like Zika and dengue from spreading. How? By competing with viruses for entry into our cells, they act like bodyguards.

What is Host Defense Mechanism System?

The host defense mechanism system is like the body’s own security team, constantly working to protect us from harmful invaders like viruses and bacteria. It’s made up of various components, including the immune system and other biological processes, that work together to detect, neutralize, and eliminate threats.

Conventional & Non-Conventional Virus Transmission

Virus transmission is a critical aspect of infectious disease spread. While conventional routes are well-known and established, non-conventional routes present unique challenges and complexities.

1. Conventional Virus Transmission:

Direct Contact Transmission:

• Transmission through direct contact with bodily fluids like saliva, blood, or respiratory droplets.
• Examples include influenza, HIV, and COVID-19.

Indirect Contact (Fomite) Transmission:

• Spread via contaminated surfaces or objects.
• Common in diseases such as the common cold and norovirus.

Vector-Borne Transmission:

• Spread through vectors like mosquitoes, ticks, or fleas.
• Diseases like malaria, dengue fever, and Lyme disease are transmitted this way.

2. Non-Conventional Virus Transmission:

Transmission via Unconventional Bodily Fluids:

• Spread through bodily fluids other than blood or respiratory secretions.
• Zika virus can be transmitted through semen, while HIV can spread through breast milk.

Airborne Transmission:

• Viruses are suspended in the air and can be inhaled by individuals nearby.
• Measles, tuberculosis, and COVID-19 (under certain conditions) can spread via airborne transmission.

Vertical Transmission:

• Transmission from mother to child during pregnancy, childbirth, or breastfeeding.
• Examples include HIV, cytomegalovirus, and Zika virus.

Key Points:

• Conventional transmission routes are well-understood and include direct contact, indirect contact (fomite), and vector-borne transmission.
• Non-conventional routes pose unique challenges, such as transmission through unconventional bodily fluids and airborne transmission.
• Understanding both conventional and non-conventional transmission is crucial for implementing effective preventive measures and controlling the spread of infectious diseases.

The Role of Cell Receptors in Viral Infection

These are the roles of cell receptors in Viral Infection:

1. Gateway to Infection: Cell receptors act as entry points for viruses, facilitating their entry into host cells.
2. Specificity: Each virus has specific receptors it recognizes and binds to, allowing for targeted infection of particular cell types.
3. Determining Tropism: The presence of specific receptors on different cell types determines the tropism of viruses, dictating which cells they can infect.
4. Initiating Viral Entry: Interaction between viral proteins and cell receptors triggers the process of viral entry into host cells.
5. Internalization Mechanisms: Cell receptors mediate various internalization mechanisms, such as receptor-mediated endocytosis or membrane fusion, facilitating viral entry.
6. Tissue Tropism: Distribution of cell receptors across tissues determines viral tissue tropism, influencing the organs and cell types susceptible to infection.
7. Viral Evolution: Viruses can evolve to adapt their receptor-binding properties, enhancing host range or virulence.
8. Emergence of Novel Strains: Changes in receptor usage contribute to the emergence of novel viral strains with altered infectivity profiles.
9. Host-Pathogen Interaction: Interaction between viral proteins and cell receptors plays a critical role in host-pathogen interactions, influencing disease outcome and pathogenesis.
10. Therapeutic Targets: Targeting viral receptors offers a potential strategy for antiviral therapy, disrupting viral entry and inhibiting infection.

Types of Cell Receptors

These are the key types of cell receptors-

1. G Protein-Coupled Receptors (GPCRs)

• These receptors are involved in a wide range of physiological processes, including sensory perception, neurotransmission, and hormone signaling.
• Activation of GPCRs initiates intracellular signaling cascades through interaction with G proteins, regulating various cellular responses.

2. Receptor Tyrosine Kinases (RTKs)

• RTKs are key players in cell growth, differentiation, and metabolism.
• Activation of RTKs leads to phosphorylation of tyrosine residues and subsequent activation of downstream signaling pathways, influencing cellular functions.

3. Ion Channel Receptors

• These receptors regulate the flow of ions across cell membranes, controlling membrane potential and cellular excitability.
• Activation of ion channel receptors by ligands or voltage changes leads to alterations in ion permeability, affecting cellular physiology.

4. Nuclear Receptors

• Nuclear receptors are transcription factors that regulate gene expression in response to ligand binding.
• Ligand binding induces conformational changes in nuclear receptors, allowing them to bind to specific DNA sequences and modulate gene transcription.

5. Cytokine Receptors

• Cytokine receptors mediate cellular responses to cytokines, which are key signaling molecules involved in immune regulation and inflammation.
• Binding of cytokines to their receptors activates intracellular signaling pathways, modulating immune cell function and inflammatory responses.

6. Toll-like Receptors (TLRs)

• TLRs are pattern recognition receptors involved in innate immune responses to microbial pathogens.
• Recognition of pathogen-associated molecular patterns by TLRs triggers immune cell activation and production of inflammatory mediators, initiating the innate immune response.

7. Integrin Receptors

• Integrins are cell adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions.
• Activation of integrin receptors regulates cell adhesion, migration, and signaling, playing crucial roles in development, immune response, and tissue homeostasis.

8. Scavenger Receptors

• Scavenger receptors are involved in the clearance of modified or foreign molecules, including pathogens and cellular debris.
• These receptors recognize a broad range of ligands and facilitate their internalization and degradation, contributing to immune defense and tissue homeostasis.

Phosphatidyl Serine Receptor

Phosphatidyl serine (PS) receptors are specialized cell surface receptors that specifically bind to phosphatidyl serine molecules, a type of phospholipid found predominantly in the inner leaflet of the cell membrane. These receptors play crucial roles in various physiological processes, including apoptosis (programmed cell death), phagocytosis (the engulfment and clearance of dying cells), and immune regulation.

Key Points about Phosphatidyl Serine (PS) Receptors:

1. Recognition of Apoptotic Cells: During apoptosis, phosphatidyl serine is translocated from the inner to the outer leaflet of the cell membrane, serving as an “eat me” signal for phagocytes. PS receptors on phagocytic cells recognize and bind to exposed phosphatidyl serine, facilitating the clearance of apoptotic cells.
2. Facilitation of Phagocytosis: Binding of phosphatidyl serine to its receptors triggers signaling cascades within phagocytic cells, leading to cytoskeletal rearrangements and engulfment of apoptotic cells into phagosomes.
3. Immune Regulation: PS receptors are involved in immune regulation by promoting anti-inflammatory responses and immune tolerance. Engagement of PS receptors on immune cells can suppress pro-inflammatory cytokine production and modulate immune cell function.
4. Role in Viral Entry: Some viruses exploit PS receptors as entry points into host cells through a process known as apoptotic mimicry. By expressing phosphatidyl serine on their surface, viruses can bind to PS receptors on target cells and gain entry into the cell, bypassing traditional viral entry mechanisms.
5. Diversity of PS Receptors: PS receptors encompass a diverse range of molecules, including members of the TAM (Tyro3, Axl, Mer) receptor tyrosine kinase family, Tim4 (T-cell immunoglobulin and mucin domain-containing molecule 4), and other scavenger receptors.
6. Clinical Implications: Dysregulation of phosphatidyl serine recognition and clearance pathways has been implicated in various diseases, including autoimmune disorders, neurodegenerative diseases, and cancer. Modulation of PS receptor signaling pathways represents a potential therapeutic target for these conditions.

What are Extracellular Vesicles?

What are they?

Extracellular vesicles (EVs) are small, membrane-bound particles released by cells into the extracellular space. They contain a variety of biomolecules, including proteins, nucleic acids (such as RNA and DNA), lipids, and metabolites. EVs are classified into different types based on their size, biogenesis pathways, and cargo composition.

Where do they locate?

Extracellular vesicles are found in various bodily fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. They can also be present in tissue microenvironments and play critical roles in intercellular communication within tissues and organs.

How do they form?

Extracellular vesicles are formed through intracellular processes, primarily through the budding and release of vesicles from the plasma membrane or through the packaging of biomolecules into vesicles within endosomal compartments. The two main types of EVs are exosomes, which are derived from the endosomal pathway, and microvesicles, which bud directly from the plasma membrane.

Role in the human body

1. Cell Communication: EVs serve as vehicles for intercellular communication, allowing cells to exchange signaling molecules, genetic material, and other bioactive molecules. They can transfer functional cargo, such as proteins and RNAs, to recipient cells, modulating various cellular processes.
2. Immune Regulation: EVs play essential roles in immune regulation, including antigen presentation, immune cell activation, and immunomodulation. They can influence both innate and adaptive immune responses, serving as mediators of immune tolerance or inflammation.
3. Tissue Homeostasis: EVs contribute to tissue homeostasis by participating in processes such as tissue repair, regeneration, and angiogenesis. They can carry growth factors, cytokines, and extracellular matrix components, influencing cellular behaviors and tissue remodeling.
4. Disease Pathogenesis: Dysregulation of extracellular vesicle secretion and cargo composition has been implicated in various diseases, including cancer, neurodegenerative disorders, cardiovascular diseases, and infectious diseases. EVs can promote disease progression by transferring oncogenic molecules, inducing immune suppression, or spreading pathogens.
5. Diagnostic and Therapeutic Potential: Due to their ability to reflect the physiological state of cells and tissues, extracellular vesicles have emerged as promising biomarkers for disease diagnosis, prognosis, and monitoring. They also hold potential as therapeutic vehicles for drug delivery, gene therapy, and regenerative medicine.

Different types of Extracellular Vesicles

There are mainly 4 types of Extracellular Vesicles:

1. Exosomes

• Origin: Exosomes are small vesicles ranging from 30 to 150 nanometers in diameter that originate from the endosomal compartment of the cell.
• Biogenesis: They are formed through the inward budding of the endosomal membrane to form multivesicular bodies (MVBs), which eventually fuse with the plasma membrane, releasing exosomes into the extracellular space.
• Cargo: Exosomes contain a diverse cargo, including proteins, lipids, RNAs (mRNA, miRNA, and other non-coding RNAs), and DNA fragments. These molecules play critical roles in intercellular communication and modulating recipient cell functions.

2. Microvesicles (also known as Microparticles or Shedding Vesicles)

• Origin: Microvesicles are larger vesicles, typically ranging from 100 to 1,000 nanometers, that bud directly from the plasma membrane of the cell.
• Biogenesis: They are formed through outward budding and shedding of vesicles from the plasma membrane in response to various stimuli or cellular activation processes.
• Cargo: Microvesicles carry a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, derived from the parent cell. They serve as mediators of intercellular communication and can influence recipient cell behavior.

3. Apoptotic Bodies

• Origin: Apoptotic bodies are larger vesicles, typically ranging from 500 to 5,000 nanometers, that are released during the process of apoptosis (programmed cell death).
• Biogenesis: They are formed through the fragmentation of the cell undergoing apoptosis, resulting in the packaging of cellular contents into membrane-bound vesicles.
• Cargo: Apoptotic bodies contain a mixture of cellular organelles, fragmented DNA, and cytoplasmic components. They serve as a means of removing dying or damaged cells and facilitate their clearance by phagocytes.

4. Ectosomes (also known as Large Vesicles or Oncosomes)

• Origin: Ectosomes are heterogeneous vesicles that vary in size and are released by budding from the plasma membrane of cells.
• Biogenesis: They are formed through outward blebbing and shedding of vesicles from the cell surface, often in response to specific cellular processes or activation signals.
• Cargo: Ectosomes carry a diverse cargo, including proteins, lipids, and nucleic acids, and can influence neighboring or distant cells through their released contents.

Breakthrough Discovery: Extracellular Vesicles as Defense

In a groundbreaking discovery, researchers have uncovered the role of extracellular vesicles (EVs) as a novel defense mechanism in the human body against viral infections. This discovery sheds light on the previously unrecognized capacity of EVs to inhibit viral transmission via non-conventional routes, offering new insights into host-pathogen interactions and immune defense strategies.

Key Findings:-

1. Identification of Defense Mechanism

Scientists have identified a previously unknown defense mechanism wherein EVs present in bodily fluids, such as saliva and semen, contain phosphatidyl serine (PS) proteins on their surface. These PS-containing EVs compete with viruses for entry into target cells, thereby inhibiting viral infection and transmission.

2. Inhibition of Viral Entry
Through a series of experiments, researchers have demonstrated that PS-containing EVs effectively compete for the same receptors used by viruses for cellular entry. By binding to these receptors, EVs effectively block viral attachment and internalization, thus preventing viral infection.

3. Broad-Spectrum Antiviral Activity

The inhibitory effect of PS-containing EVs extends to a range of viruses that utilize PS receptors for entry, including Zika virus, dengue virus, chikungunya virus, West Nile virus, Ebola virus, and vesicular stomatitis virus. This broad-spectrum antiviral activity highlights the potential of EVs as a versatile  defense mechanism against viral pathogens.

4. Implications for Immune Defense

The discovery of EVs as a defense mechanism against viral infections has significant implications for our understanding of immune defense strategies. EVs not only play a role in intercellular communication but also contribute to innate immune responses by limiting viral spread and infection.

5. Therapeutic Potential

While further research is needed to fully elucidate the therapeutic implications of this discovery, the identification of EVs as natural antiviral agents opens up new avenues for the development of novel therapeutic strategies. Harnessing the antiviral properties of EVs could lead to the development of innovative approaches for combating viral infections and enhancing immune defense mechanisms.

Mechanism of Viral Infection Inhibition

The mechanism of viral infection inhibition by extracellular vesicles (EVs), particularly those containing phosphatidyl serine (PS) proteins on their surface, involves several key steps aimed at blocking viral entry and replication. This process represents a novel defense mechanism utilized by the human body to counteract viral infections and limit their spread.

Below are the details of the mechanism:

1. Competition for Cell Receptors: PS-containing EVs compete with viruses for binding to cell surface receptors that are utilized by the viruses for cellular entry. By binding to these receptors, EVs effectively block the attachment and internalization of viruses into host cells, thus preventing viral infection.
2. PS Receptor-Mediated Inhibition: Many viruses, including Zika virus, dengue virus, chikungunya virus, and others, exploit PS receptors for entry into target cells. PS-containing EVs present in bodily fluids contain PS proteins on their surface, which can bind to PS receptors on host cells. This interaction interferes with the ability of viruses to engage with PS receptors, thereby inhibiting viral entry and infection.
3. Crowding Out Effect: The presence of abundant PS-containing EVs in bodily fluids creates a competitive environment for viral particles seeking entry into host cells. The high concentration of EVs effectively “crowds out” the viruses, reducing their ability to interact with host cell receptors and decreasing the likelihood of successful viral infection.
4. Broad-Spectrum Antiviral Activity: The inhibitory effect of PS-containing EVs extends to a broad range of viruses that utilize PS receptors for entry. This broad-spectrum antiviral activity makes EVs a versatile defense mechanism against various viral pathogens, including Zika virus, dengue virus, chikungunya virus, West Nile virus, Ebola virus, and vesicular stomatitis virus.
5. Immune Modulation: In addition to directly blocking viral entry, EVs may also modulate immune responses to further inhibit viral infection. EVs can carry immunomodulatory molecules and signaling factors that regulate immune cell functions, suppress inflammation, and enhance antiviral immunity, contributing to the overall defense against viral infections.

Implications for Immune Response and Viral Defense

The discovery of extracellular vesicles (EVs), particularly those containing phosphatidyl serine (PS) proteins, as a defense mechanism against viral infections has profound implications for immune response modulation and viral defense strategies. Understanding the role of EVs in viral defense enhances our knowledge of host-pathogen interactions and opens up new avenues for therapeutic interventions. Here are the key implications:

1. Enhanced Antiviral Immunity: EVs play a crucial role in modulating immune responses against viral infections. By inhibiting viral entry and spread, EVs contribute to the containment of viral pathogens within the host. This enhances the effectiveness of the immune system in detecting and eliminating viral invaders.
2. Natural Defense Mechanism: The identification of EVs as natural antiviral agents highlights the sophistication of the human immune system in combating viral infections. EVs represent a built-in defense mechanism that operates at the interface of innate and adaptive immunity, providing an additional layer of protection against viral pathogens.
3. Broad-Spectrum Antiviral Activity: The inhibitory effect of PS-containing EVs extends to a wide range of viruses, including Zika virus, dengue virus, chikungunya virus, and others. This broad-spectrum antiviral activity underscores the versatility of EVs as innate immune effectors capable of targeting multiple viral pathogens simultaneously.
4. Potential Therapeutic Applications: Harnessing the antiviral properties of EVs holds promise for the development of novel therapeutic strategies against viral infections. EV-based therapies could include the administration of exogenous EVs or the modulation of endogenous EV production to enhance host defense mechanisms and limit viral replication and spread.
5. Immune Modulation: EVs not only directly inhibit viral infection but also modulate immune responses to further enhance viral defense. EVs can carry immunomodulatory molecules that regulate the activity of immune cells, suppress inflammation, and promote antiviral immunity, contributing to the overall defense against viral pathogens.
6. Future Research Directions: Further research into the mechanisms underlying EV-mediated viral defense is needed to fully elucidate their therapeutic potential. Investigating the interplay between EVs and viral pathogens, as well as their interactions with the host immune system, will provide valuable insights into the development of EV-based antiviral therapies and immune modulation strategies.

Exploring Viral Tropism and Host Interaction

Understanding how viruses infect our bodies and how our bodies respond is crucial for fighting diseases. Here’s a simpler explanation:

Viral Tropism

• What is it?: Viruses have preferences for certain cells or tissues they infect. This is called viral tropism.
• How does it work?: Each virus has specific proteins that fit like keys into certain locks on our cells. When the key fits, the virus can get in and cause infection.
• Examples: Some viruses target our lungs, like the flu virus, while others, like herpes, target nerve cells.

Host Interaction

• Cell Receptors: Our cells have receptors that viruses use to enter. For example, HIV uses receptors on immune cells to get inside.
• Immune Responses: Our immune system fights viruses. It has ways to detect and destroy them, but viruses can sometimes trick our immune system or weaken it.
• Viral Evasion: Viruses can use tricks to hide from our immune system or stop it from working properly. This helps them survive and spread in our bodies.
• Host Factors: Things like our genes, age, and health affect how we respond to viruses. Some people might get sicker from a virus because of their genes or health conditions.

Research Strategies

• Experimental Models: Researchers use experimental models, including cell culture systems, animal models, and clinical studies, to investigate viral tropism and host interactions. These models allow researchers to study the molecular mechanisms of viral infection, test antiviral therapies, and develop vaccines.
• Genomic and Proteomic Analysis: Genomic and proteomic techniques, such as next-generation sequencing and mass spectrometry, enable researchers to identify viral receptors, host factors, and immune responses involved in viral infection. These approaches provide valuable insights into virus-host interactions at the molecular level.
• Systems Biology Approaches: Systems biology approaches, including mathematical modeling and network analysis, help integrate complex datasets and elucidate the dynamics of viral tropism, host responses, and viral pathogenesis. These computational methods aid in predicting viral behavior, identifying therapeutic targets, and designing interventions.

Different types of Host Defense Strategies

These are the key types of Host Defense Strategies:

1. Physical Barriers: Our bodies have physical barriers like skin and mucous membranes that stop viruses from getting inside.
2. Innate Immunity: This is our body’s quick response to invaders. It includes things like fever, inflammation, and special cells that attack viruses right away.
3. Adaptive Immunity: This is our body’s long-term defense. It makes antibodies that remember viruses and fight them off if they come back.
4. Cellular Defense: Special cells in our body, like macrophages and natural killer cells, hunt down and destroy viruses.
5. Interferons: These are proteins that our cells release to warn nearby cells about a viral attack, helping them prepare to fight off the virus.
6. Complement System: This is a group of proteins in our blood that work together to kill viruses and infected cells.

PS-Coated Vesicles

What are PS-Coated Vesicles?

• PS-coated vesicles are tiny structures enclosed by fat molecules (lipids) found in bodily fluids like saliva and semen.
• These vesicles contain phosphatidylserine (PS) proteins on their surface, which are normally associated with signaling cell death to the immune system.

Role in Host Defense

• Recent research has uncovered that PS-coated vesicles serve as a defense mechanism against certain viruses, including Zika and dengue viruses.
• These vesicles compete with viruses for entry into host cells by binding to the same receptors that viruses use for attachment and entry.

Mechanism of Action

• PS-coated vesicles mimic dying cells by displaying PS proteins on their surface, which act as decoy targets for viruses.
• When viruses encounter PS-coated vesicles, they mistakenly bind to these vesicles instead of host cells, preventing viral entry and infection.

Research Findings

• Studies have shown that PS-coated vesicles are abundant in bodily fluids such as saliva and semen, where viruses like Zika are present but rarely transmitted through non-conventional routes.
• Experimental evidence suggests that these vesicles effectively inhibit viral infection by blocking viral attachment and entry into host cells.

Implications for Viral Defense

• The discovery of PS-coated vesicles as a natural defense mechanism sheds light on new strategies to prevent viral transmission.
• Understanding how these vesicles interfere with viral entry could lead to the development of novel antiviral therapies and preventive measures.

Future Directions

• Further research is needed to elucidate the precise mechanisms by which PS-coated vesicles inhibit viral infection and to explore their potential therapeutic applications.
• Investigating the role of these vesicles in other viral infections and understanding their interaction with the immune system could uncover additional insights into host defense mechanisms.

FAQs – Extracellular Vesicles UPSC Questions

Question-1: What are extracellular vesicles and how do they function in the body’s defense against viruses?

Answer. Extracellular vesicles are small lipid-enclosed structures containing phosphatidyl serine (PS) proteins on their surface. They compete with viruses for entry into host cells, thereby inhibiting viral attachment and infection.

Question-2: How do extracellular vesicles differ from conventional immune responses?

Answer. Unlike conventional immune responses, which rely on direct immune cell action, extracellular vesicles act as decoys, intercepting viruses before they can infect host cells.

Question-3: What viruses are targeted by the extracellular vesicle defense mechanism?

Answer. The extracellular vesicle defense mechanism inhibits viruses that utilize the PS receptor for entry, including Zika, dengue, chikungunya, West Nile, Ebola, and vesicular stomatitis viruses.

Question-4: How do extracellular vesicles affect viral transmission in bodily fluids like saliva and semen?

Answer. Extracellular vesicles containing PS proteins are abundant in bodily fluids, such as saliva and semen, where they compete with viruses for entry into host cells, effectively reducing viral transmission via non-conventional routes.

Question-5: What are the potential therapeutic implications of this discovery?

Answer. This discovery opens avenues for the development of novel antiviral therapies targeting viral entry mechanisms. Additionally, it may inform the design of vaccines and preventive measures against emerging viral threats.

Question-6: How do PS-coated vesicles influence the evolution of mosquito-borne viruses?

Answer. PS-coated vesicles may have influenced the evolution of mosquito-borne viruses by restricting their transmission through bodily fluids like saliva and semen, thereby prompting the viruses to adapt alternative transmission routes.

Question-7: Are extracellular vesicles present in other bodily fluids besides saliva and semen?

Answer. Yes, extracellular vesicles containing PS proteins are found in various bodily fluids, including breast milk and blood plasma, although their concentrations may vary.

Question-8: Can extracellular vesicles be harnessed for diagnostic purposes?

Answer. While current research primarily focuses on the therapeutic potential of extracellular vesicles, their diagnostic applications, such as biomarkers for viral infections, warrant further investigation.

Question-9: What challenges lie ahead in translating this discovery into clinical applications?

Answer. Challenges include elucidating the precise mechanisms underlying extracellular vesicle-mediated viral inhibition, optimizing delivery strategies for therapeutic interventions, and addressing potential off-target effects.

Question-10: How does this discovery contribute to our understanding of host-virus interactions?

Answer. This discovery provides valuable insights into host-virus interactions, highlighting the sophisticated defense mechanisms employed by the human body to combat viral infections.