HOST DEFENCE AGAINST ZIKA, DENGUE VIRUSES

Source: Hindu

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Context

• The discovery of a novel defense mechanism against Zika and other viruses sheds light on the intricate interactions between viruses and the human body's immune system.

Details

Background

• Transmission Challenge: Despite the presence of Zika, dengue, and chikungunya viruses in bodily fluids like saliva and semen, they do not typically spread orally or sexually, puzzling scientists for years.
• Role of Receptors: Viruses utilize specific surface proteins to interact with receptors on host cells, facilitating their entry and infection.
• Apoptotic Mimicry: Viruses exploit the Phosphatidyl Serine (PS) receptor pathway, which is usually used by immune cells to recognize and destroy dying cells, allowing them to infect cells that express this receptor.

What does a virus do inside the body?

Inside the body, viruses undergo a series of steps to establish infection and replicate:

Entry into Host Cells:

• Viruses enter the body through various routes, such as inhalation, ingestion, or transmission through bodily fluids like blood or semen.
• Once inside the host, viruses must gain entry into target cells to initiate infection.

Attachment and Entry:

• Viruses have specific surface proteins that recognize and bind to receptors on the surface of host cells. This binding triggers the entry of the virus into the cell.
• Each virus has a particular cell tropism, meaning it can only infect certain types of cells that express the appropriate receptor.

Replication:

• After entry, the virus releases its genetic material (RNA or DNA) into the host cell.
• The viral genetic material hijacks the host cell's machinery to replicate itself, producing viral proteins and new viral particles.

Assembly and Release:

• New viral particles are assembled inside the host cell.
• These particles may bud off from the cell membrane, causing the host cell to burst (lysis), or they may be released through a process called exocytosis.

Spread and Transmission:

• Once released from infected cells, viruses can spread to neighboring cells and tissues, amplifying the infection.
• Viral transmission to new hosts can occur through various routes, including respiratory droplets, bodily fluids, or vector-borne transmission by insects like mosquitoes.

Novel Defense Mechanism

• Extracellular Vesicles (EVs): EVs are small structures released by cells, containing various substances. Researchers discovered that EVs in bodily fluids like saliva and semen contain PS proteins on their surface.
• Competition with Viruses: Through experiments, it was demonstrated that these PS-containing EVs compete with viruses for the same receptors, effectively crowding them out and preventing infection.

Implications

• Broad Antiviral Effect: The presence of PS-coated EVs inhibits not only Zika but also other viruses like dengue, chikungunya, West Nile, ebola, and vesicular stomatitis viruses that use the PS receptor for entry.
• Therapeutic Potential: While it's too early to speculate on therapeutic applications, this discovery opens avenues for further research into potential treatments or preventive measures against viral infections.

About Dengue Fever

• Dengue fever is a mosquito-borne viral infection caused by the dengue virus (DENV).
• It is prevalent in tropical and subtropical regions worldwide, with significant outbreaks occurring in Asia, the Americas, Africa, and the Western Pacific.
• Dengue fever is classified into four serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, all belonging to the Flaviviridae family.
• Dengue fever is a major public health concern, with an estimated 100-400 million infections occurring annually worldwide.
• The incidence has increased dramatically over the past few decades, leading to a higher frequency of severe cases and outbreaks.
• Endemic in over 100 countries, primarily in tropical and subtropical regions where Aedes mosquitoes, particularly Aedes aegypti and Aedes albopictus, thrive.

Symptoms:

• Dengue fever can manifest as a spectrum of symptoms, ranging from mild flu-like illness to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).
• Common symptoms include high fever, severe headache, joint and muscle pain, rash, and mild bleeding manifestations (e.g., nosebleeds, gum bleeding).
• Severe dengue, characterized by plasma leakage leading to fluid accumulation, severe bleeding, and organ impairment, can be life-threatening without prompt medical intervention.
• Warning signs include persistent vomiting, abdominal pain, mucosal bleeding, lethargy, and hepatomegaly.

Diagnosis:

• Diagnosis is primarily based on clinical symptoms, epidemiological factors (e.g., recent travel to endemic areas), and laboratory confirmation through tests such as NS1 antigen detection, RT-PCR, or serological assays to detect IgM and IgG antibodies.

Treatment:

• There is no specific antiviral therapy for dengue fever.
• Treatment involves supportive care to manage symptoms, maintain hydration, and monitor for signs of severe dengue, with timely intervention in a hospital setting if necessary.
• Several dengue vaccine candidates are under development, with the first licensed vaccine, Dengvaxia, approved in some countries.
• As of 2023, there are two commercially available vaccines, sold under the brand names Dengvaxia and Qdenga.
• Ongoing research aims to improve vaccine efficacy, safety, and coverage to address the complex challenges of dengue prevention.

About Zika Virus

• Zika virus (ZIKV) is a mosquito-borne flavivirus first identified in the Zika Forest of Uganda in 1947.
• It gained global attention during the outbreak in Brazil in 2015 due to its association with congenital disabilities like microcephaly and Guillain-Barré syndrome.
• Primarily transmitted through the bite of infected Aedes mosquitoes, particularly Aedes aegypti and Aedes albopictus.
• Can also spread through sexual contact, blood transfusion, and from mother to fetus during pregnancy.
• Major outbreaks occurred in various regions, including the Americas, Pacific Islands, and Southeast Asia.
• Initially found in Africa and Asia, it has since spread to other regions due to globalization and climate change.
• Present in tropical and subtropical areas worldwide, including parts of Africa, Southeast Asia, the Pacific Islands, and the Americas.

Symptoms:

• Most infected individuals remain asymptomatic or experience mild symptoms such as fever, rash, joint pain, and conjunctivitis.
• Severe complications include neurological disorders like Guillain-Barré syndrome in adults and congenital malformations such as microcephaly in babies born to infected mothers.

Congenital Zika Syndrome (CZS):

• Infants born to mothers infected with Zika virus during pregnancy may develop CZS, characterized by severe neurological defects, including microcephaly, seizures, and developmental delays.

Diagnosis:

• Diagnostic tests include reverse transcription-polymerase chain reaction (RT-PCR), serological assays, and nucleic acid tests to detect viral RNA or antibodies.
• Differential diagnosis may include other mosquito-borne diseases like dengue and chikungunya.

Treatment:

• No specific antiviral therapy is available for Zika virus infection.
• Treatment mainly focuses on managing symptoms, such as fever and pain, with rest, fluids, and analgesics.

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Sources:

Hindu

PRACTICE QUESTION Q.  Discuss the strategies employed by viruses to establish infection and transmit to new hosts. How do these strategies interact with the host immune response? Explain with relevant examples. (250 Words)