Introduction to Virology

Introduction to Virology

• Virology is the study of viruses.

Viral Structure, Classification, and Replication

• Virus properties:
• They are obligate intracellular parasites
• Viruses cannot make energy or proteins
• Their genomes can be RNA or DNA, but not both
• They have either a naked capsid or an envelope
• Viral components assemble but do not replicate by division

Virus Structure: General Features

• Nucleocapsid is either helical or icosahedral
• The viral genome is either DNA or RNA
• Viruses contain structural proteins, enzymes, and nucleic acid-binding proteins
• Naked capsid viruses consist of just the nucleocapsid
• Enveloped viruses contain a nucleocapsid, membrane, and glycoproteins

Properties Based on Virus Structure

• Naked capsid viruses are stable to environmental conditions, easily spread, retain infectivity after drying, and are released through cell lysis
• Enveloped viruses are labile, need to stay wet to spread, are inactivated if dried out, and are released through cell lysis and budding

Viral Genomes

• Most viruses contain either single-stranded RNA or double-stranded DNA
• Some DNA viruses have single-stranded DNA
• Most viruses are haploid, but retroviruses are diploid

Classification of Viruses

• DNA viruses can be enveloped or non-enveloped, and can be single or double-stranded, and circular or linear
• RNA viruses can also be enveloped or non-enveloped, positive or negative sense, and may be segmented
• Positive-sense RNA is identical to DNA, while negative-sense is complementary to DNA
• Retroviruses are classified separately due to their unique replication method

Steps of Viral Replication

• Attachment and recognition occur, where the virus enters through receptor-mediated endocytosis
• The virus uncoats and releases its genome
• Synthesis of protein and nucleic acids occurs
• Macromolecular synthesis occurs
• The virus assembles and the cell undergoes lysis or budding to release the virus

Viral Entry and Budding

• Entry type depends on the host cell and its membrane proteins
• Uncoating can occur on the cell membrane, within endosomes, or at the nuclear membrane
• Budding involves the viral membrane becoming part of the cell membrane, allowing persistent infection and immune evasion
• Enveloped viruses that do not kill the host cell require a stronger immune response

Replication of DNA Viruses

• DNA viruses enter the nucleus after uncoating
• Macromolecular synthesis occurs with early genes (non-structural), genome replication, and late genes (structural)
• Assembly occurs in the nucleus
• Virus is released through cell lysis
• Poxviruses replicate in the cytoplasm and Hepadnavirus (Hepatitis B) uses an RNA intermediate

Replication of Positive-Strand (+) RNA Viruses

• The RNA uncoats and stays in cytoplasm
• Genome is used as mRNA
• Polyprotein is expressed
• Polyprotein is cleaved
• RNA polymerase is activated
• Replication of the genome occurs
• Assembly occurs in in the cytoplasm
• Example of exception: Retrovirus which uses DNA Intermediate

Replication of Negative-Strand (-) RNA Viruses

• RNA polymerase is coded within the RNA strand.
• Uncoating is required
• Protein and sense RNA are synthesized
• Genome is replicated and released.

Viral Genetics and Evolution

• Viral evolution can be rapid through recombination, reassortment (genetic shift), or slower through mutations (genetic drift)
• Mutations result from errors in copying the viral genome
• These mutations can lead to antiviral resistance or altered antigenicity, and can increase pathogenesis
• Recombination involves a single virus gaining new genetic material when replicating
• Reassortment is specific to influenza.

SARS-CoV-2 origin

• SARS-CoV-2 origin via recombination with both bat and pangolin coronavirus sequences in one viruses

Viral Pathogenesis

• Viral pathogenesis results from the interaction of viral and host factors leading to disease production
• Patterns of viral infection include abortive, acute, and persistent infections
• Persistent infections can be latent, chronic, or transforming

Steps of Viral Pathogenesis

• Viral entry can occur through the skin, respiratory tract, gastrointestinal tract, urogenital tract, conjunctiva, blood, or through vertical transmission (mother to baby)
• modes of transmissions

Modes of Transmission

• Direct: via contact, aerosol (respiratory), or sexual transmission (HSV) or physical (mouth to mouth- EBV and skin-VZV)
• Indirect: through fecal-oral route
• Transmission from animal to human- zoonotic -rabbies, hantavirus, coronavirus
• The means of arthropod vectors -mosquitos/garrapatas

Primary Viral Replication

• Locally at the site of entry (catarrh) or systemically and disseminated.
• Hematogenous - lymphatic system to bloodstream Cellular Injury and Clinical Illness.
• Tissue Tropism
• The Viral shedding, the capacity to cause disease, is virulent not killed, and not attenuated
• Prevention and Treatment are key

Virus Vaccines

• Can be used for prevention and control of viral infections
• Can be common like inated or attenuated, or special situations, live and killsd

Antivirals Overview

• Antivirals should aim to target steps in the viral replication differ cellular processes such as: Penetration, Uncoating, Genome Replication and Release
• May be non or more specific
• May or may not need integration into the Host DNA

Interferons

• Interferons are released from infected cells and confer resistance to infection in neighboring cells to induce fever.
• Inhibits cell growth, replication and activate macrophages and other parts of innate immunity
• These bind to DNA and cells

What is Ribavirin?

• It is a nucleoside analog similar in structure to deoxyguanosine
• Ribavirin impairs the synthesis of GTP thus reducing pools and RNA activity
• It has a board antiviral toxicity
• The triphosphate form of ribavirin also increases DNA and RNA
• Has Limited use due to high toxicity

HPV: Human Papillomaviruses

• It is a common STD with about 150 serotypes
• It has a Naked icosahedral capsid and it circular
• It can replicates in skin and mucous membrane
• Codes for early proteins that inactivates p53 (E6) and RB (E7)

HPV Disease Types: Human Papillomavirus

• Lesions Associated with Human Papillomavirus, like; planar, common warts, or cancer
• Transmission direct an sexual and to treat you need; salicylic acid and surgical removal
• In can can be 90% precented, or anal an vaginal
• HPV Nonavalent is; Gardasil 6® Merck, low risk and 6 / 11 and highisk 16 / 18, , 31, 33, 45, 52, 58

Herpesviruses Overview

• Double strainded DNA
• Includes Herpes simplex 1/2,
• Varicella Zoster , Epstein-Barr,
• Cytomegalovirus
• Human Herpes
• Has Lytic and Persistent Infections

HSV

• Occurs for the Skin / Eyes and CNS cells
• Reactivation to the sacral and trigeminal
• Can be traeted
• Treat with Acyclovir or antivirals

VZV: (Varicella Zoster)

• The treatment is to lower Reactivation with age
• Has latency effect
• Has Treatment = Acyclovir, foscarned and for children
• Has attenuated virux for chickenz

Acyclovir Action Mode

• It is a nucleoside and used to treat Varicella and Herpes.
• must be has a thymidine
• After integration with the virus that block 3 phoshate
• Acyclovir reduces shedding

Cytomegalovirus CMV

• Can be spread, is an infection from monoucleuous
• Can occur by affecting Infects Cells, Endothelial cells,
• Treat via ganciclovir

Ganciclovir and Cytomeglovirus

• Is similar structure as deoxy
• must be phoshorylated

EBV: Epstein

Can occur because is a Herpes Family

• There is not treatment, but Mononucleus
• Diagnosit is Monotet and can do liver checks

Hepadnaviruses & Cirrhosis Overview

The examples: Includes Hepatitis B It is Enveloped with icosahedral capsid

• Circular, partially ds DNA and associated woth polymerase and also RNA
• Symptoms occur by having liver disease and abnormalities
• Infected during blood transmissions