---

Structure of a Virus

---

1. Core Components

A. Viral Nucleic Acid (Genome)

• Every virus contains one type of nucleic acid only - either DNA or RNA, never both.
• The genome may be:
  • Single-stranded (ss) or double-stranded (ds)
  • Linear or circular
  • Segmented (multiple pieces, e.g., influenza) or nonsegmented (single piece)
• DNA genome size: 3.2 kbp (hepatitis B / hepadnaviruses) up to 375 kbp (poxviruses)
• RNA genome size: ~4 kb (picobirnaviruses) up to 32 kb (coronaviruses)
• Polarity matters:
  • Positive-sense RNA (e.g., picornaviruses, togaviruses) - the isolated RNA is itself infectious and acts directly as mRNA
  • Negative-sense RNA (e.g., orthomyxoviruses/influenza, rhabdoviruses) - isolated RNA is NOT infectious; requires a packaged RNA polymerase to first make mRNA copies

B. Capsid (Protein Coat)

• The capsid is a protein shell surrounding and protecting the genome from nucleases and the environment.
• Built from repeating protein subunits called capsomeres (and individual folded polypeptides called subunits).
• Functions:
  • Protects viral nucleic acid
  • Mediates attachment to host cell receptors
  • Determines antigenic characteristics (the immune response targets capsid/surface proteins)
• The nucleocapsid = nucleic acid + capsid together

C. Capsid Symmetry - Three Types

---

2. Viral Proteins

• Transfer the genome from one host cell to another
• Protect the genome against nucleases
• Attach to host cell receptors (e.g., influenza hemagglutinin binds sialic acid)
• Carry enzymatic activities - some virions package essential enzymes:
  • RNA polymerase (negative-sense RNA viruses - must make mRNA before replication begins)
  • Reverse transcriptase (retroviruses - converts RNA genome into DNA)
  • Transcriptional machinery (poxviruses - entire transcription system packaged inside the core)
• Antigenic determinants - the host immune system targets surface proteins/glycoproteins

---

3. Viral Lipid Envelope (Present in Some Viruses)

• The envelope is a lipid bilayer derived from the host cell membrane, acquired when the nucleocapsid buds out through the cell membrane during maturation.
• Budding occurs only where virus-specific proteins have been inserted into the host membrane.
• The phospholipid composition of the envelope reflects the host cell membrane (not virus-coded).
• Glycoproteins (virus-coded) are embedded in the envelope and project as spikes:
  • Examples: influenza hemagglutinin (HA) and neuraminidase (NA)
  • These are the key surface antigens recognized by the immune system

• Enveloped viruses are generally more fragile - they are inactivated by lipid solvents (ether, detergents)
• Non-enveloped viruses are hardier and can survive harsh environments (gut acid, desiccation)

---

4. Virus Size

---

5. Summary Diagram (Conceptual)

NON-ENVELOPED VIRUS           ENVELOPED VIRUS
+------------------+         +---------------------+
|   Capsid         |         | Envelope (lipid)    |
|  [Capsomeres]    |         |  + Glycoprotein      |
|                  |         |    spikes (HA, NA)  |
|  Nucleic Acid    |         |  Nucleocapsid inside|
|  (DNA or RNA)    |         |  (Nucleic acid +    |
|                  |         |   capsid proteins)  |
+------------------+         +---------------------+
e.g., Poliovirus              e.g., Influenza, HIV

---

---

The Virion = The Complete Virus Particle

"Virus" is the general biological concept (like saying "a dog"). "Virion" is the specific, complete physical particle (like saying "this particular dog standing in front of you").

"Virion: The complete virus particle... this structure serves to transfer the viral nucleic acid from one cell to another."

---

What the Virion Contains (Inside → Outside)

---

Two Types of Virions

[Nucleic acid] → [Capsid] = Virion
(the nucleocapsid alone IS the complete virion)

[Nucleic acid] → [Capsid] → [Envelope + spikes] = Virion
(all three layers together make the complete virion)

---

Where the Virion Exists

• Outside cell = Virion (complete, infectious particle)
• Inside cell = The virus has uncoated and the genome is actively replicating

---

---

Virion = Complete Virus Particle = (Usually) Infectious

---

1. Virion = Complete, but not always infectious

• Defective - structurally intact but carrying a mutated/incomplete genome, so they cannot replicate
• Inactivated - physically complete but their genome or surface proteins have been damaged (by heat, UV light, antibodies), making them non-infectious

---

2. Virus inside a cell is NOT called a virion

---

Simple Way to Remember It

---

---

Classification of Viruses

1. ICTV Taxonomic System - based on structure and genome
2. Baltimore Classification - based on how the virus makes mRNA

---

System 1 - ICTV Taxonomy (Structural Classification)

• Family: suffix -viridae (e.g., Herpesviridae)
• Subfamily: suffix -virinae (e.g., Herpesvirinae)
• Genus: suffix -virus (e.g., Herpesvirus)
• Species: common name (e.g., herpes simplex virus 1)

---

System 2 - Baltimore Classification (7 Groups)

Key rule: Positive-sense RNA (+ssRNA) acts directly as mRNA. Negative-sense RNA (-ssRNA) needs its own RNA polymerase packaged in the virion to first make mRNA.

---

Classification by Genome Type

RNA Viruses Infecting Humans

---

DNA Viruses Infecting Humans

---

Quick Summary - How to Remember

DNA Viruses (mnemonic: "Please Have Some Pretty Hot Popcorn"):
  Parvo → Hepadna → Polyoma → Papilloma → Adeno → Herpes → Pox

RNA Viruses (positive-sense = naked tend to be; enveloped tend to be negative/RT):
  Naked (+): Picorna, Calici, Reo, Astro, Hepe
  Enveloped (+): Flavi, Toga, Corona
  Enveloped (-): Paramyxo, Orthomyxo, Rhabdo, Filo, Bunya, Arena
  RT (Enveloped): Retro (RNA→DNA), Hepadna (DNA→RNA→DNA)

---

---

For MBBS Exams - Priority Guide

Baltimore Classification - Higher Priority

• Asked directly in exams: "Which group does HIV belong to?", "Classify HBV", "Positive-sense RNA viruses"
• Helps you understand replication - which is tested heavily in microbiology practicals and theory
• Only 7 groups - easy to memorize
• Explains WHY certain viruses behave differently (e.g., why HIV needs reverse transcriptase, why influenza needs its own RNA polymerase)
• Forms the conceptual backbone for understanding antiviral drugs (e.g., reverse transcriptase inhibitors for Group VI)

ICTV Classification - Also Required, but More as Reference

• You need to know family names (-viridae) and which viruses belong to which family
• Directly tested as: "Hepatitis B belongs to which family?" (Hepadnaviridae), "Rabies belongs to?" (Rhabdoviridae)
• The full table is not memorized - used as a reference, as Sherris & Ryan explicitly states: "The tables should not be memorized but rather used as a reference guide"
• Important for identifying structural features - naked vs enveloped, size, symmetry

---

What MBBS Students Actually Need to Know

---

Bottom Line

Learn Baltimore first - it gives you the logic. Then layer ICTV family names on top. Together they cover ~90% of virology questions in MBBS exams (1st Prof Microbiology, and clinical years).

---

Baltimore Classification - Full Explanation

The Core Idea

Every virus must produce mRNA. Why? Because viruses have no ribosomes. They MUST use the host cell's ribosomes to make proteins. Ribosomes only read mRNA. So no matter what genome a virus has - DNA or RNA - it must get to mRNA somehow.

---

The Concept of Polarity (+ and - Sense)

---

The 7 Baltimore Groups

---

GROUP I - Double-Stranded DNA (dsDNA)

dsDNA  →[transcription]→  mRNA  →[translation]→  Proteins

• Genome: Two strands of DNA (like our own chromosomes)
• Replication: Goes into the nucleus, uses host DNA-dependent RNA polymerase to make mRNA - just like normal cells do
• Highly dependent on host cell cycle - cell must be dividing for many of these
• Examples: Herpesviruses (HSV, VZV, CMV, EBV), Adenoviruses, Papillomaviruses (HPV), Polyomaviruses, Poxviruses (exception: replicates in cytoplasm, carries its own enzymes)

---

GROUP II - Single-Stranded DNA (ssDNA)

ssDNA  →[DNA polymerase]→  dsDNA  →[transcription]→  mRNA

• Genome: Only ONE strand of DNA
• Must first make a complementary strand to become dsDNA, THEN transcribe mRNA
• Smallest DNA viruses
• Examples: Parvoviruses (Parvovirus B19 - causes fifth disease / slapped cheek), Anelloviruses (TT virus)

---

GROUP III - Double-Stranded RNA (dsRNA)

dsRNA  →[viral RNA polymerase]→  mRNA  (positive strand)

• Genome: Two strands of RNA
• Cannot use host enzymes (host has no RNA-dependent RNA polymerase)
• Must carry their own RNA polymerase packaged inside the virion
• Replication occurs inside the capsid core in the cytoplasm (never in nucleus)
• Genome is usually segmented (multiple pieces)
• Examples: Reoviruses, Rotavirus (major cause of childhood diarrhea)

---

GROUP IV - Positive-Sense Single-Stranded RNA (+ssRNA)

(+)ssRNA  =  mRNA directly  →[translation]→  Proteins
             ↓[RNA-dependent RNA polymerase made]
           (-)ssRNA intermediate  →  more (+)ssRNA copies

• Genome IS the mRNA - ribosomes can read it immediately upon cell entry
• Most infectious isolated RNA (inject the RNA alone into a cell = infection)
• First thing that happens: genome gets translated into a polyprotein, which includes an RNA-dependent RNA polymerase (RdRp) for replication
• Largest group - most human RNA viruses are positive sense
• Examples:
  • Picornaviridae: Poliovirus, HAV, Rhinovirus (common cold), Coxsackievirus
  • Flaviviridae: Dengue, Zika, Yellow fever, West Nile, Hepatitis C (HCV)
  • Togaviridae: Rubella, Chikungunya
  • Coronaviridae: SARS-CoV-2, MERS, common cold coronaviruses
  • Caliciviridae: Norovirus

---

GROUP V - Negative-Sense Single-Stranded RNA (-ssRNA)

(-)ssRNA  →[viral RNA polymerase]→  mRNA (+)  →[translation]→  Proteins

• Genome CANNOT be read directly - it is the complement/mirror image of mRNA
• MUST carry RNA-dependent RNA polymerase (RdRp) packaged inside the virion - without it, the genome is useless
• Isolated RNA from these viruses is non-infectious
• Often have segmented genomes (influenza has 8 segments - key fact for exams!)
• Examples:
  • Orthomyxoviridae: Influenza A, B (8 segments - replicates in nucleus, unique among RNA viruses)
  • Paramyxoviridae: Measles, Mumps, RSV, Parainfluenza
  • Rhabdoviridae: Rabies (bullet-shaped)
  • Filoviridae: Ebola, Marburg (filamentous)
  • Bunyaviridae: Hantavirus, Crimean-Congo hemorrhagic fever

---

GROUP VI - ssRNA with Reverse Transcriptase (ssRNA-RT)

(+)ssRNA  →[Reverse Transcriptase]→  DNA  →[integrates into host genome]→  mRNA

• Retroviruses - unique because they go RNA → DNA (reverse of normal flow of genetic information)
• Carry reverse transcriptase (RT) and integrase in the virion
• After RT makes DNA copy, it integrates permanently into host chromosome as a provirus
• Host cell then transcribes it like its own gene → viral mRNA and proteins
• Genome is diploid (2 copies of RNA per virion)
• Examples: HIV-1, HIV-2 (causes AIDS), HTLV-1 (causes T-cell leukemia)
• Clinical importance: All anti-HIV drugs (NRTIs, NNRTIs) target reverse transcriptase

---

GROUP VII - dsDNA with Reverse Transcriptase (dsDNA-RT)

dsDNA  →[transcription]→  pregenomic RNA  →[Reverse Transcriptase]→  new dsDNA

• Most unusual group - DNA virus that uses reverse transcription in its replication cycle
• Goes DNA → RNA → DNA (uses an RNA intermediate called pregenomic RNA)
• Also carries reverse transcriptase
• Only one major human pathogen in this group
• Example: Hepatitis B virus (HBV) - Hepadnaviridae
• Clinical importance: Why HBV can integrate into the genome; why it can persist even after treatment; why drugs like tenofovir (an RT inhibitor) work against HBV

---

Summary Table - All 7 Groups

---

Memory Aid for MBBS

"Don't Stupid People Really Never Read Books"
 D     S    P     R     N    R    B
 I    II   IV    III    V   VI   VII
dsDNA ssDNA +RNA  dsRNA -RNA RT-RNA RT-DNA

• Groups I & II = DNA viruses
• Groups III, IV, V = Pure RNA viruses
• Groups VI & VII = Reverse transcriptase viruses (RNA↔DNA)

---

Most Commonly Tested in MBBS

1. HIV = Group VI (RT, integrase, diploid)
2. HBV = Group VII (dsDNA but uses RT - "DNA virus that behaves like a retrovirus")
3. Influenza = Group V (8 segments, carries RdRp, replicates in nucleus)
4. Poliovirus/Rotavirus/Rhinovirus = Group IV/III
5. Rabies = Group V (-ssRNA, bullet shape)
6. COVID-19 = Group IV (+ssRNA, largest RNA genome)

---

Baltimore Does NOT Classify Families

---

What Each System Actually Does

---

Think of It This Way

Baltimore = sorting people by blood group (A, B, AB, O) - a functional property, not physical appearance

ICTV = sorting people by nationality - based on origin, features, shared characteristics

---

So for MBBS - Use Both Together

• When asked "classify HIV" → Give BOTH: "HIV belongs to Baltimore Group VI (ssRNA-RT) and family Retroviridae"
• When asked "which family does influenza belong to?" → ICTV answer: Orthomyxoviridae
• When asked "classify influenza by genome" → Baltimore answer: Group V, negative-sense ssRNA

---

Positive Sense vs Negative Sense RNA

First - Understand mRNA

---

Positive Sense (+) RNA

Same sequence as mRNA

• The viral genome RNA reads exactly like mRNA
• Ribosomes can grab it and translate it directly into proteins the moment it enters the cell
• No extra step needed
• The genome itself IS the mRNA

Viral (+) RNA enters cell
        ↓
Ribosome reads it directly
        ↓
Viral proteins made immediately

• Isolated (+) RNA is infectious on its own - inject it into a cell, infection begins
• Does NOT need to carry an RNA polymerase in the virion (because no conversion needed at first)
• Fastest to start infection - proteins made immediately

---

Negative Sense (-) RNA

Complementary (mirror) to mRNA - opposite/antiparallel

• The viral genome RNA is the exact opposite of mRNA
• Ribosomes cannot read it - it is like a template strand, not a coding strand
• Must first be converted into positive-sense mRNA before anything can happen
• Needs an enzyme to do this conversion: RNA-dependent RNA polymerase (RdRp)
• This RdRp must be packaged inside the virion - because the host cell has no such enzyme

Viral (-) RNA enters cell
        ↓
RdRp (brought in the virion) converts it
        ↓
(+) mRNA produced
        ↓
Ribosome reads mRNA → Viral proteins

• Isolated (-) RNA is NOT infectious - without the packaged RdRp, it cannot be read
• Must carry RdRp in the virion - this is a defining feature
• Slightly slower to start infection (extra conversion step)

---

Side-by-Side Comparison

---

Simple Memory Trick

• (+) sense = the book is printed normally - you open it and read immediately
• (-) sense = the book is printed in mirror image - you need a mirror (RdRp) before you can read it

• (+) sense = the final photograph (what you see)
• (-) sense = the photographic negative (you need to develop/convert it first)

---

What About Ambisense?

---

Why This Matters Clinically

• Influenza (-ssRNA): Its RdRp is the target of baloxavir (a newer anti-influenza drug)
• HIV (+ssRNA): Goes RNA → DNA via reverse transcriptase - its RT is targeted by NRTIs and NNRTIs
• HCV (+ssRNA): Its RdRp is targeted by sofosbuvir (a direct-acting antiviral)
• Understanding polarity helps you predict which antivirals work on which virus

---

The Genetic Code - How Ribosomes Read mRNA

The Rule: Codons

• mRNA is made of 4 bases: A, U, G, C
• Every 3 bases = 1 codon
• Each codon codes for one specific amino acid
• This is the genetic code - fixed, universal, and non-overlapping

---

The Complete Genetic Code

---

The Fixed Rules of the Code

1. Start Codon - AUG

• Every mRNA must start with AUG (codes for Methionine)
• This is where the ribosome begins reading
• Without AUG, the ribosome cannot start

2. Stop Codons - UAA, UAG, UGA

• These three codons do not code for any amino acid
• When the ribosome hits one of these, it stops and releases the protein
• Called nonsense codons

3. Reading Frame

• The ribosome reads one codon at a time, left to right, without overlap
• The starting point (AUG) sets the reading frame - shift by even one base and the whole meaning changes

---

How Translation Works (Step by Step)

mRNA:  5'---AUG---UUU---CAG---UAA---3'
            MET   PHE   GLN   STOP

Ribosome reads left to right, 3 bases at a time
→ Makes protein: Methionine - Phenylalanine - Glutamine → Released

"The tRNA recognizes the proper spot to attach on the mRNA template because it has on its active end a set of three bases (anticodon) that are complementary to a set of three bases (codon) on the mRNA chain."

---

Now - Back to Positive vs Negative Sense

---

Properties of the Genetic Code (Important for Exams)

---

Why Viruses Exploit This

• A viral mRNA (or +sense RNA genome) placed inside a human cell gets translated perfectly
• The ribosome cannot distinguish "self" mRNA from "viral" mRNA - same code, same rules
• This is the fundamental trick of viral infection