Virology

General Properties of Viruses

What is virus?
The smallest infectious and acellular microbe.
Consisting only one kind of nucleic acid (DNA or RNA), and which obligately replicate inside host cells.

 Virions
The complete mature viral particles.
(The intact infectious virus particles.)

Distinctive features

• The simplest: acellular microbes contain either DNA or RNA
• The smallest: Pas through 0.2μm filters                      
• Obligatory intracellular parasites.
• Self-replication

 I. Size, shape and structure
  A. Size 
     The unit of measurement nm

Comparative sizes of virions and bacteria

1. Staphylococcus aureus
2. Rickettsia
3. Chlamydia
4. Poxviruses
5. Bacteriophage of E. coli
6. Influenza virus
7. Adenovirus
8. Encephalitis B virus
9. Poliovirus

B. Shape
Tobacco mosaic virus: rod-shaped

Poxvirus: brick-shaped 

HIV:Spherical

VSV (Vesicular stomatitis virus): bullet-shaped

Bacteriophage T4: tadpole-shaped

Ebola Virus: filamentous shape

C.Structure
Basic structure:
Core: Viral nucleic acid  (DNA or RNA)
Capsid: Protein shell
capsomers (morphological subunit)
polypeptide molecules (chemical subunit)

Core + Capsid → nucleocapsid

Size, shape and structure
Naked virus:
Virion: nucleocapsid.

Enveloped virus:
Virion: nucleocapsid+Envelope
spikes (peplomers);
Others: enzymes, etc.
e.g. Retrovirus has reverse transcriptase

Symmetry of  viral nucleocapsids: Is decided by arrangement of capsomeres
Helical symmetry
(e.g., tobacco mosaic virus)
Icosahedral symmetry
(e.g., adenovirus)
Complex symmetry
(e.g., poxviruses )

Chemical composition
Viral nucleic acid: ssDNA, dsDNA, ssRNA, dsRNA
Viral proteins:
 protection, mediate the attachment of virue to specific receptors on host cell surface
 determine species and organ specificity
 important antigens, superantigen

Unconventional viruses
Viroid
plant disease
Human Hepatitis D
NOTE: a single circular RNA molecule without a protein coat which mainly cause plant diseases.

Prion
Proteinaceous infectious particle
Human diseases:
     e.g., Kuru
Animal diseases:
e.g.,Scrapie
     Bovine spongiform encephalopathy (BSE)
NOTE: infectious agents composed of a single glycoprotein with MW 27-30 kDa.

II. Replication
In host cell, virus replicates its nucleic acid and synthesizes
its proteins, then assembles them to form progeny viral
particles that are released by budding or cell lysis.

Replication---Normal Replication

• Adsorption /Attachment
• Penetration 
• Uncoating 
• Biosynthesis
• Assembly 
• Release 

i. Adsorption / Attachment
Specific binding of a viral attachment protein (VAP) with a receptor on the surface of host cell;
VAP (on virion ) --- viral surface protein
Spike – enveloped virus
Capsid protein – naked virus
Viral receptor (on host cell)
Glycoprotein, carbohydrate or glycolipid
    e.g., CD4 (HIV), CD46 (measles virus), Sialic acid (influenza virus)
Tropism

Adsorption/Attachment

ii. Penetration
Mechanisms:
A. Endocytosis
Some enveloped viruses
Most naked virus

B. Direct fusion of cell membrane with viral envelope:
Only enveloped viruses

C. Nucleic acid translocation:
Some bacteriophages and naked virus

iii. Uncoating
The process of removing capsid and releasing viral nucleic acid into the cytoplasm;
Acidification of the content of the endosome
Proteases are needed;

iv. Biosynthesis
 Eclipse phase
 Biosynthesis includes:

•  Viral genome replication
•  Viral protein synthesis

The replication strategy depends on the nature of viral genome.
dsDNA;   ssDNA;   dsRNA;   +ssRNA;   -ssRNA; retrovirus
+ssRNA with DNA intermediate in life cycle (HIV);
dsDNA with RNA intermediate (HBV);

Biosynthesis

+ssRNA virus (Poliovirus, HAV)
 Viral genomic RNA serve as mRNA;
 Enzymes for replication are made after infection, not carried in virion;
 (Extracted) Viral genomic RNA is infectious

-ssRNA virus e.g., influenza virus
 Virion carries RDRP;
 First step: Transcription of viral genome;
 Extracted -ssRNA not infectious;

v. Assembly
Naked virus:    capsid + viral genome → nucleocapsid (virion, complete structure)
Enveloped virus: capsid + viral genome → nucleocapsid (incomplete structure)
Site:
a. DNA viruses (except poxvirus): cell nucleus;
b. RNA viruses and poxvirus: cell cytoplasm;
Manner:
a. assemble as empty shell (procapsid), then viral genome fill in.    
b. Viral capsomeres array around the viral genome to form helical
    symmetry.

vi. Release
The process of progeny viruses getting out of host cell.

Naked viruses:released by cell lysis.
Enveloped viruses:usually released by budding.
During budding enveloped viruses acquire their envelope.
Defective measles virus: release from cell to cell via cell bridges.

enveloped virus replication （1）

enveloped virus replication （2a）
     

     
enveloped virus replication （2b）

enveloped virus replication （3）

enveloped virus replication （4）

 Abnormal replication
Two aspect factors:
Viruses
Defective viruses
Host cells
non-permissive cells → Abortive infection

Defective viruses
are genetically deficient and incapable of producing infectious progeny virions.
Helper virus
can supplement the genetic deficiency and make defective viruses replicate progeny virions when they simultaneously infect host cell with defective viruses.
e.g., HDV & HBV

• Defective viruses lack gene(s) necessary for a complete infectious cycle;
• helper viruses provide missing functions;

• 100:1 (defective to infectious particles)
• DIP (defective interfering particle) : When the defective viruses can not replicate, but can interfere other congeneric mature virion entering the cells, we call them defective interfering particles (DIP).

Abortive infection:
Virus infection which does not produce infectious progeny because the host cell cannot provide the enzyme, energy or materials required for the viral replication.
non-permissive cells
The host cells that cannot provide the conditions for viral replication.
permissive cells
The host cells that can provide the conditions for viral replication.

 III. Viral interference:
 
   When two viruses infect simultaneously one host cell, One type of virus
    may inhibit replication of another type of virus.
 
Range of interference occurrence

•  between the different species of viruses;
•  between the same species of viruses;
•  between the inactivated viruses and live viruses.

Main mechanisms of viral interference:
a. One type of virus inhibit or prevent subsequent adsorption and penetration
    of another virus by blocking or destroying receptors on host cell.
b. The competition of two viruses for replication materials, e.g., receptor
    polymerase, translation initiation factors, etc.
c. One type of virus may induce the infected cell to produce interferon that
    can prevent viral replication.
       
The mechanism of IFN function 

Significance of viral interference:
Advantage
    a. Stop viral replication and lead to patient recovery.
    b. Inactivated virus or live attenuated virus can be used as vaccine to
        interfere with the infection of the virulent virus.
Disadvantage
 May decrease the function of vaccine when bivalent/trivalent vaccine is used.

Just for your practice see the answers at the end.
Fill in the blank
1-The surrounding protein coat of a virus is called the _______   and it is composed of protein subunits called _________.      
2-Viruses that are only covered with a protein coat outside viral genome are called ______ viruses, while those that have an additional lipid-containing membrane covering are called ________ viruses.
3. The general steps of the viral replication cycle include ( in the order of their occurrence) ___________________, ___________, ____________, __________, _________________.

ANSWERS

1-Capsid. Capsomeres.

2-Naked, Enveloped.

3-Attachment, Penetration, Uncoating, Biosynthesis, Assembly and release.