Flaviviridae and Dengue Virus

Flaviviridae

• Enveloped viruses that range in diameter from 40-60 nm.
• Positive single-stranded RNA viruses.
• Mature virions accumulate in the endoplasmic reticulum cisternae.
• Part of the Arbovirus group, including Dengue and Yellow Fever viruses.
• Primarily transmitted by blood-sucking arthropods as mosquito-borne human pathogens
  • Transmitted by vectors like Aedes aegypti and Aedes albopictus.
• Mostly found in tropical and subtropical climates, such as Southeast Asia and the Caribbean.

Dengue

• Characterized by virions that are about 50 nm in diameter.
• Virions contain two virus-encoded membrane-associated proteins, like E protein

Clinical Features of Dengue

• Can range from asymptomatic to life-threatening.
• Incubation lasts around 3-14 days.
• It progresses in three stages
  • Febrile: lasts approximately 2-7 days and includes symptoms such as an acute or sudden onset of HG fever (24 hours to 3 weeks)
• Additional symptoms: headaches, myalgia, and arthralgia.
• Also retro-orbital pain, nausea, vomiting, rashes, and occasional abdominal pain may occur.
• Occurs after fever has subsided.
• Lasts for 24-48 hours.
• Thrombocytopenia (low platelet count).

Dengue Hemorrhagic Fever

• Marked by hematemesis, melena, and epistaxis.

Dengue Shock Syndrome

• Causes intravascular leakage due to inflammatory cytokines, resulting in hypotension and circulatory shock.
• Organ system impairment, especially CNS deficits, acute kidney injury, and liver damage

Recovery from Dengue

• Decreased vascular permeability.
• Vital signs normalization.
• Weakness remains significant.

Transmission of Dengue

• Occurs through the bite of infected mosquitoes, specifically Aedes aegypti and Aedes albopictus.
• Mosquitoes lay eggs in stagnant water.
• Spreads during daytime and nighttime.
• Mosquitoes can be infected through infected persons with dengue and spreads the infection through bites

Pathogenesis of Dengue

• Begins with an infected mosquito bite.
• The virus attaches to the epidermis and fuses with the cell using its E viral glycoprotein.
• The virus binds to viral receptors and enters the host cell.
• It is then packaged into an endosome - acidified vacuole.
• Viral RNA forms through viral disassembly
• Intracellular replication
• Viral particles then assemble in the endoplasmic reticulum
• The virus matures into a virion in the endoplasmic reticulum and Golgi apparatus.
• Finally, it is packaged for release, infecting other cells.

Diagnosis of Dengue

• Dengue NS1 antigen detection is effective within 1-5 days of illness.
• Helps to detect the acute phase.
• Dengue IgM/IgG antibody detection is useful beyond five days of illness.
  • May cross-react with Zika virus or other flaviviruses.
• PCR -considered the gold standard for confirming dengue.
• Routine blood tests
  • Increased hematocrit as well as decreased WBC and platelet counts may provide an indication of dengue.

Treatment and Prevention of Dengue

• Treatment is primarily supportive, using paracetamol, increased fluid intake, and bed rest.
  • Anti-biotics not advisable without other infections
  • Avoid use of ibuprofen and aspirin for this condition due to anti-coagulation properties
• Preventive aims: use mosquito repellent, protective clothing, eliminate sources of stagnant water, use bed nets, and secure windows and doors.
• Vaccination available (Dengvaxia).
• It requires a three-dose series.
• Each shot is spread over six months, and can be administered for people 9-45 years old

Japanese Encephalitis

• Closely resembles dengue.
• Leading cause of encephalitis in Asia.
• Responsible for childhood infections.
• May lead to permanent damage

Characteristics of Japanese Encephalitis

• Diameter of 40-50 nm.
• Contains single-stranded RNA.
• Spherical with a cubical symmetry morphology.

Clinical Features of Japanese Encephalitis

• Can range from asymptomatic to life-threatening.
• Incubation periods ranges from 4-14 days
• High grade fevers and headaches.
• Additional symptoms: neck stiffness, nausea, and vomiting.
• Can cause brain infections
  • Symptoms include disorientation, coma, seizures, and spastic paralysis
• May lead to complications such as neurologic impairment, behavioral issues, speech deficits, paralysis, and recurrent seizures.

Transmission of Japanese Encephalitis

• Occurs through mosquito bites, such as Culex sp.
• Birds/pigs also risk infection following mosquito bites
• Humans are dead-end hosts and cannot transmit

Diagnosis of Japanese Encephalitis

• Conducting IgM-capture ELISA through JEV-specific IgM antibodies within the CSF or serum
• MRI for brain lesions

Treatment and Prevention of Japanese Encephalitis

• treatment approach provides support, including administration of paracetamol.
• Increase fluid intake along with bed rest.
• Preventive measures

Pathogenesis of Japanese Encephalitis

• Infected mosquito bites.
• the person’s blood and subsequent viremia, or the parasites entering the person’s macrophages instead
• The disease then enters the blood-brain barrier; can also influence pons
• Damage may affect basal ganglia, thalamus and midbrain

Togaviridae (Chikungunya)

• Alphavirus from the Togaviridae virus
• Enveloped viruses of spherical Morphology
• Contains a single-stranded RNA virus.
• Diameter: 70 nm.
• Contains single capsid protein and 3 glycoproteins
• Most are mosquito-borne

Transmission of Chikungunya

• It is transferred to humans by mosquito bites - such as from Aedes aegypti and Aedes albopictus
• Humans serve as essential hosts
• Vertical Transmission of blood by the mom to the infant is possible

Chikungunya pathogenesis

• Occurs after mosquitoes bite

Chikungunya Clinical Features

• Incubation period (3-7 days)
• Mostly Symptomatic
• High Temperature
• Sharp onset of temperature
• Joint pain
• Muscle pain

Chikungunya Symptoms

• Cephalgia
• Eye inflammation
• Vomiting / Nausea
• Maculopapular rash
• Reduced lymphocytes
• Thrombocytopenia
• Elevated liver enzyme

Diagnosing Chikungunya

• Perform viral culture within the first 3 days after contamination
• Conduct PCR for viral presence during the first week

Coronaviridae (SARS CoV-2)

• Contains RNA
• 6 Functional Open reading frames can form and arrange as 3'-5'

Coronaviridae SARS Cov-2 Virus Characteristics

• A newly-discovered virus in Corona
• The first incident was reported in China (2019, December) with signs of an outbreak
• Found in populations residing in Wuhan City at a wet market
• Originated from SARS CoV with the ecological origin in Bats + Pangolins
• The Genetic Order was discovered in early Jan
• Contains spike S protein

Transmission of SARS CoV-2

• It Spreads through droplets from the respiratory tract
• Transmission can occur Airborne - up to 1 meter
• It spreads if the public gathers
• spreads by bodily contact

SARS-CoV-2 pathogenesis

• Sars-CoV enters the Alveoli from the respiratory tract
• Attaches to type 2 pneumocytes
• Spike converts proteins + binds to ACE II enzymes
• mRNA translates + ribosomes use bodies proteins

Signs of Coronaviridae SARS-Cov-2 Virus

• Primary signs are related to taste alterations, respiratory problems, chills, temperature + muscular pain

Coronaviridae - SARS CoV-2 Treatment and Diagnoses

• Sample is taken via nose + throat
• Do a PCR
• If negative, repeat after 3 days
• Administer supportive treatment; hydrate + keep Pt stable
• Isolate Patient
• Use Paracetamol
• Treat with steroid medication (Dexamethasone)
• If SpO2 is less than 94 Administer Oxygen

Coronavirus - SARS-CoV-2 Diagnostic measures

• Test blood - check for antibodies

Coronavirus - SARS-CoV-2 Prevention

• Vaccinate - Moderna & Phizer
• Practice self care - wear hygiene equipment + wash frequently

Clinical Symptoms for Influenzavirus

• Chills + fatigue
• Can cause fever

Characteristics for Influenzavirus

• Common viral respiratory illness

Transmission of Influenza Virus

• Enters through mucus-membranes due to droplets from sneezing/coughing
• Via direct contacts - saliva from another person

Treatment for Flu Virus

• Administer antiviral medication
• Use zanamivir

Life Cycle for Flu Virus in Hosts

• Binds to terminal on upper resp. cells (epithelial cells)
• Releases Genetic materials into Host (Viral RNA)
• Surface proteins use Host DNA to replicate
• Exits + releases from cell
• Attracts immune + cytokine cells

Characteristics of Rabies Virus

• It originates from the family Rhabdovilidae
• It is bullet-shaped
• Its genomic material can be described as as single-stranded RNA, Non- segmented

Effects + Pathology due to rabies virus.

• Infection transmitted via animal bite
• Travels into nerve to spinal ganglia
• Moves towards CNS (spinal cord + brain) + replicates rapidly
• Travels to salivary + other organs for further replication

Signs + Symptoms of Rabies Virus.

• Fever + fatigue
• Breathing problems
• Nausea Vomiting
• Abdominal pain
• Dysphagia; difficulty in speaking or saying words with ease, aphasia
• Excitation Stage may manifest in some
• Can cause anxiety + agitation
• Can cause Photo or Hydraphobia.

Characteristics for Poliovirus

• Caused/Related to Small Picornaviridae viruses
• Three Types, Types 1, 2 + 3
• Causes Paralysis
• Single stranded infection

Virus + Pathology (polio)

• Transmitted Via Food/Water- contamination
• Enters the tract and replicates
• Results in Systemic infection may occurs via bloodstream

Poliovirus Signs and symptoms. (Clinical Features)

• Last 1-10 Days for about 3-6 incubation
• Causes Stiff neck
• may lead to meningitis or sensory-motor deficits

Treating + Diagnosing Polio

• Isolate Patient and diagnose via viral smear test
• Can get via blood test
• Can also get in other cultures (via stool samples or spinal fluid)
• Sanitation helps

Polio, HIV Retroviridae Virus + Pathology

• HIV genus consists of ‘Lentivirus’
• This virus is a global concern that causes aids
• Contains RNA Material
• Has specific receptors that attach and attack cells - > CD4 cells

Characteristics for HIV Virus

• Reverse transcriptase enables genetic material in hosts
• Enveloped- attacks
• Leads to Immunodeficiency via decreasing levels of CD4 in cells

Transmission of HIV Virus

• Via fluid exposure, blood, sexual reproduction
• Vertical transmission can occur (from Breast milk)

Viral Proteins responsible for Infection in Hosts (HIV)

• Viral Protein-Gp120
• A vital protein important for attachment to membrane
• Essential for entry inside
• Gp41; essential for viral infections + has a protein complex
• P17- responsible for coating cell and makes proteins
• P24 - vital for capsid layer/development

Signs + Stages HIV Patients

• Patients in Stage 1 are extremely contagious
• They show flu-like symptoms
• In 2nd (asymptomatic stage) patients may have minor symptoms
• Progression occurs without Treatment
• Stage 3(AIDS) - most severe, + causes opportunistic infections
• Immune suppressed, and <200CD4 count
• Survival rate ~ 3 years without intervention
  • CD4 count = 500+ normal, <200 Low

HIV Virus diagnostics - clinical lab measures

• Run PCR & Viral amplification tests
• Antigen-Antibody blood Tests

Clinical Treatment of the effects due to HIV-Virus -

• Use drug combo as therapy to ‘slow down' infection
• Integrase inhibitors can assist in the process in CD4 T Cell Infection
  • NRTI are supportive during replication

Pathology of prions

• The infection/pathology comes via infection and transfer via tissues
• This infection is capable thru routes involving ingestion or contact
• Causes long incubation along with vacuoles

Characteristics for Prions

• No immune activation and proteins are misfolded, resistant to disinfectants
• Long Term incubation needed

Risks Caused by Prions

• CJD- Risk factors and GGS are factors that cause various geography seasonal changes
• This leads to death

Signs and Symptoms caused by Prion infection

• Produces Sleep problems and anxiety
• Motor and muscle loss
• Affect coordination - causes tremors
• In-voluntary jerks
• Can only confirm at autopsy
• Rapid progression leading to cognitive decline

Diagnosing Prion based infection - clinical lab data

• Prions Dont trigger Serologic responses, diagnosis can vary via clinical data (but not limited to)
• Need to run scans and do protein analysis to confirm

Pathology Caused by Prion Aggregates

• Amyloid plaque deposits
• Induces neurotoxic responses that cause progressive neuron degradation

Treatment and Measures for prion based pathologies:

• There is currently no way to treat + reduce it's effects because it has a long time impact