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Medical Virology Part 1

Virus
Small obligate intracellular parasites → need a living host for survival

smallest among the MO

500 million Rhinoviruses (CA of the common cold) could fit on the head of a pin

NOT living organism

only alive and able to multiply when they are inside a living host

use the machinery of the host cell to replicate

Acellular

Has no other organelle except CHON and nucleic acid (either RNA or DNA)

Do NOT replicate → viral replication only happens when virus-infected cell

replicates

considered inert (inactive) outside the host

Unable to generate energy

as an obligate intracellular parasite, during replication, they fully depend on

the complicated biochemical machinery of the host cell for transcription and
translation processes

cant produce ATP on their own and have to use the machinery of the host cell
(eukaryotic or prokaryotic)

the main purpose of the virus is to deliver its viral genome into the host cell to
allow its expression

Viral Morphology
Three Integral Components

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 Nucleic Acid Core → DNA or RNA

DNA — deoxyribonucleic acid

RNA — ribonucleic acid

green strands of DNA/RNA

Capsid / CHON coat

protects the nucleic acid core

dictates the symmetry or shape of the virus

Capsomere → basic unit of capsid

each bead of the capsid

blue spheres encircling the nucleic acid core

Viral envelope

glycoprotein envelope

pink and green

types

(+) enveloped

(-) naked virus

Other components: Surface CHON

orange spheres

help the virus attach to its host cell

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 Viral Structure — Overview

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 complete virus particle — virion

mature viral particle composed of a nucleic acid, protein coat, which may be
surrounded by an envelope

the form in which the virus moves between cells going from one cell to another

Definitions
Bacteriophage

A virus that infects prokaryotic (bacterial) cells.

Nucleocapsid

viral nucleic acid + the protein coat that encloses it

Represents the packaged form of the viral genome

Viral Structure
Varies in size, shape & symmetry

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 morphology

3 types of capsid symmetry:

Cubic (icosahedral)

Has 20 faces, each an equilateral triangle

nucleocapsid of many spherical viruses

Eg. adenovirus

Helical

The protein binds around DNA/RNA in a helical fashion

nucleocapsids of many filamentous and pleomorphic viruses

consists of a helical array of capsids or proteins wrapped around a helical

filament of NA

eg. Coronavirus

Complex

Is neither cubic nor helical

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 often symmetrical or asymmetrical in combination w other structures such
as a tail

eg. poxvirus

some bacteriophages have a complex structure consisting of an icosahedral

head bound to its helical tail

the helical tail has a hexagonal base plate w protruding protein tail fibers

the tail structure acts as a molecular syringe

when they attach to a bacterial host, they will be able to inject their viral genome

Virus Sizes

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 Viral sizes are determined by an electron microscope

viruses normally range from 20 — 300 nm in diameter (max. 1000nm)

Viral Structure

(a) bullet-shaped virus of rabies

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 Classification and Taxonomy of Viruses
International Committee on Taxonomy of Viruses (ICTV)

is tasked with developing, refining, and maintaining a universal virus

taxonomy

viruses are not classified into the 3 domains of life cuz they are not cellular

their number is great enough to require a classification

viruses are not species, but they belong to a species

they don't have a binomial nomenclature cuz they are acellular and arent
living

classified into families and genera based on viral genetics, chemistry, morphology,
and mechanism of multiplication.

To date, there are seven orders, 96 families, and 350 genera of viruses (ICTV).

family names end in viridae (e.g. Parvoviridae) and genus names end in virus
(e.g. Parvovirus)

common names — dengue virus, poliovirus — are not italicized

when virus names are capitalized, they are italicized

it is permissible to use acronyms (e.g. West Nile Virus) after defining it

if you are going to mention the virus several times

define → abbreviate (e.g. WNV)

not italicized acronym

DNA and RNA Viruses

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 disease-causing viruses

21 virus families infecting humans, showing some distinct characteristics

not exhaustive

+ sensed, - sensed, ds, ss

letter C denotes the number of capsomeres present in the capsid

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 28 virus families infecting humans and animals

Virion
Mature viral particle

Complete virus particle:

nucleic acid + protein coat, which may be surrounded by an envelope

It is the form in which the virus moves between cells or hosts

Viral Genome
EITHER RNA or DNA genome (never both) surrounded by a protective virus-
coded protein coat (capsid)

Propagation depends on specialized host cells supplying the machinery for

replication, metabolism, and biosynthesis

The DNA or RNA genome may be :

ss — single-stranded or;

ds — double-stranded

Genomes may be either:

(+) sense

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 Positive-sense viral RNA is identical to viral mRNA and thus can be
immediately translated into protein by the host cell.

(-) sense

Negative-sense viral RNA is complementary to mRNA and thus must be

converted to positive-sense RNA by an RNA polymerase before
translation

will not directly proceed to the translation

needs a specific RNA polymerase to be converted to its + sense before

it goes to the translation process

for RNA to replicate, it has to unwind and break apart with the use of RNA
polymerase

transcription → the upper strand will be the template strand from where a single
strand of RNA containing the complementary base pairs come into play — mRNA

transcription happens in the nucleus

no thymine in the RNA strand

mRNA na agad ang + sensed

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 translation → mRNA will go to the cytoplasm of the cell

for it to produce protein, it will go to the ribosome carrying the codons — the series
of 3 bases carrying the code and it will be read by the tRNA containing the anti-
codons, which will code for a specific amino acid

1 bead = 1 amino acid

production of protein

Viral Life Cycle

Latent Stage (Lysogenic cycle)

No symptoms

Infected cells are not killed or lysed

happens wherein there is a replication of the viral genome w/o the death of the
cell

replication process in prokaryotes happens in the cytoplasm

the virus injects its viral genome and the viral genome becomes part of the
DNA of the bacteria

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 when the bacteria replicates, the viral genome also replicates w/o
killing the cell

Lytic Stage (Virulent stage)

Symptoms manifest

With lysis or destruction of infected cells

phage DNA replicates in the cell, and once the viruses are matured enough and
great in number, the cell will break and undergo lysis releasing the newly
matured virion

Viral Replication
When a virus infects a cell, nucleic acid must be uncoated and gain access to the
metabolic machinery of cells.

ATTACHMENT

PENETRATION

with the entry of nucleic acid into the cell

early EXPRESSION of virus genes

either directly by translation, if the virus contains "+" RNA, or indirectly after
transcription and then translation

BIOSYNTHESIS

REPLICATION of virus nucleic acid

SYNTHESIS of new virion components

MATURATION

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 PACKAGING and ASSEMBLY of new virions

RELEASE/ EXIT from cell

I. Attachment
specific binding of a virion protein (receptor) to a constituent of the cell
surface (anti-receptor)

attachment is a chemical interaction where a bonding must be formed within the

attachment site or receptor site

there has to be a weak bonding or interaction formed in the receptor site for
viruses

if no receptor site = no penetration or entry

in the host cell, there are diff receptors to which viruses can bind to

some viruses are very tissue-specific → tissue tropism

viruses only infect certain types of cells within tissues

e.g. Coronavirus

infects the URS and LRS

the SARSCoV-2 virus is specific to its receptor — ACE 2 receptor

(Angiotensin Converting Enzyme 2 receptor) found in the lungs

e.g. Poliovirus

exhibits tropism in the tissues of the brain, spinal cord

e.g. Influenza virus

hemagglutinin of influenza virus

H1N1 → H = hemagglutinin

infects the respiratory tract

receptor → Sialic acid

some complex viruses (e.g. HSV) may have more than one species of anti-
receptor molecule

e.g. Retrovirus → HIV

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 the receptor is the CD4 T-cells

16 other diff receptors for this virus to enter the cell

e.g. HSV

multiple receptors

II. Penetration/Entry
energy-dependent step occurs almost instantaneously after attachment

After the virus attaches to the host cell, it can enter the cell by several mechanisms:

Transfer of the entire viral particle across the cell membrane by endocytosis
(phagocytosis)

the whole virus will be engulfed by the cell

Transfer of only the viral genome through the cell membrane

bacteriophage will use its molecular syringe to inject the viral genome
needed for replication

Fusion of the viral envelope with the host cell membrane

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 III-V. Uncoating, Replication, Biosynthesis
the separation of the viral nucleic acid from its protein coat once the virion is
enclosed within the vesicle (uncoating)

at the same time as penetration or shortly after it has already separated from its
protein coat

separation of viral nucleic acid from outer structural components

Expression of viral genome and synthesis of viral component

replicate through the process of transcription and translation using the

machinery of the host cell

After the viral nucleic acid is released inside the host cell:

The transcription and translation processes of the host cell are redirected
for the production of viral proteins and nucleic acids

grabbing the machinery of the cell to produce its own genome

overriding the production of the host’s protein and NA production

The different types of nucleic acid genomes are expressed and replicated in
several ways:

DNA genomes undergo replication using processes similar to cellular

replication

RNA genomes may be +ssRNA

Can be read directly as an mRNA

go directly to the ribosomes of the cell and replicate to produce the

proteins necessary for the proliferation of the virus

can be reverse transcribed by reverse transcriptase into DNA

RNA genomes may also be -ssRNA

The RNA must first be used as a template to form +mRNAs

VI-VII. Assembly and Release

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 viruses have matured and have all the components it needs before they will be
released by the host cell

Components of capsid synthesis directed by late genes

3 classes of genes in the phage genome that is regulating whether the process
is lysogenic or lytic

immediate early gene

delayed early gene

late gene

one that determines whether the process of release is through budding

(no cell death) or through the lysis of the cell

The assembly of enveloped viruses needs interaction with the plasma membrane
which has been modified

enveloped viruses will use the plasma membrane of the host cell that was
redirected already to form the envelope of this virus

The final stage of infection

Enveloped viruses are released gradually by budding or exocytosis

Naked viruses accumulate in the cytoplasm and are released during lysis

assembly

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 a complete and mature virion comprised of a viral NA core, protein coating, and
envelope (if enveloped virus)

Unconventional Virus
incomplete viruses

slow infections cuz normally asymptomatic ung incubation period

will take a long period of time for it to be incubated and become infectious

Viroids

ss RNA genome and the smallest known pathogens

Affects plants

rarely cause disease in humans

Hepatitis D is caused by RNA small viroids

Prions

Infectious particles that are entirely protein

No nucleic acid

Highly heat resistant

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 Animal or human disease that affects nervous tissue

Affects nervous tissue and results in

Bovine spongiform encephalitis (BSE) — “mad cow disease”

scrapie in sheep

Kuru (tribes that practice cannibalism) → Creutzfeld-Jakob Disease

(CJD) in humans

if infected yung kinakain nila, pede matransfer ung virus (or viral
genome)

Viral DNA
2 Types

(+) stranded → readily transcribed

(-) stranded → ignored → convert first to its + form

Generally, DNA virus is double-stranded except for Parvovirus → only single-

stranded
DNA virus

General Property of DNA virus

Double-stranded

most are Icosahedral

Replicate in the nucleus

EXCEPTIONS:

Parvovirus → single-stranded

Poxvirus → complex symmetry; replicates in the cytoplasm

Naked DNA → Parvovirus, Adenovirus, Papovirus

Enveloped DNA → Poxvirus, Herpes virus, Hepatitis

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 Viral RNA
3 Types:

(+) stranded

Can function directly without activation as an RNA

(-) stranded

Require activation by the enzyme RNA-dependent RNA polymerase

(RDRP)

the enzyme that converts the (-) sensed strand to (+) sensed before it
can produce proteins as an mRNA

Retro RNA

behaves backward from the original way we think abt genetics

Can reverse the process of transcription

DNA → RNA

normal process

mRNA → ribosomes → protein synthesis

DNAv ← RNAv

RNA is reverse-transcribed to DNA

DNA is then inserted into the genome of the host, so when the cell
divides, it will copy this and begin to express RNA

some RNA is translated into proteins before being packaged

enzyme: reverse transcriptase

e.g. Retrovirus → HIV

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 mahirap ieradicate

(+) single-stranded RNA virus

Generally, RNA is single-stranded except for Reovirus → the only double

stranded
RNA virus

Retrovirus carry enzyme reverse transcriptase, integrase, and other viral proteins

reverse transcriptase will convert ss RNA → ss DNA

ss DNA → ds DNA and will be incorporated into the DNA of the host cell

every time the cell replicates, it is also replicating the viral DNA

difficult to be eradicated cuz its DNA is incorporated into the DNA of the host

General Property of RNA virus

Single-stranded

Helical → spherical

Enveloped

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 Replication in the cytoplasm

EXCEPTIONS:

Reovirus → double-stranded → Respiratory Enteric Orphan Virus

Rabies virus → helical-bullet shape

Naked RNA → Picornavirus, Reovirus, Calicivirus

Replicates in the nucleus → Retrovirus, Orthomyxovirus, Influenza virus

Antiviral Drugs
mostly analogs of purines and pyrimidines

can inhibit the nucleic acid synthesis

mostly pro-drugs

must be phosphorylated by the viral or cellular enzyme in order to be active

initially inactive

most antiviral drugs prevent active replication of the virus

viral agents inhibit active replication so the viral growth resumes after drug
removal when there are still viruses in the body (resume replication)

HIV therapy

need to keep the viral load low

Mechanism of Action of Antiviral Drugs

Inhibition of penetration of host cell

Amantadine and Rimantadine

inhibit uncoating

effective against influenza A virus

MOA → inhibits the ion channel activity of the M2 protein

necessary for the uncoating of the viral genome during infection

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 when amantadine and rimantadine bind to the M2 protein (yellow green) →
prevent the release or uncoating of the viral genome → will not replicate

Gamma Globulins

“neutralize viruses”

neutralization is the reduction of the effect of a component, of a virus, a

bacteria, or any toxin

an antigen-antibody reaction that aids in reducing the effect of the

viral agent

neutralize → render the pathogen inactive

booster shots → increases the number of neutralizing antibodies

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 like immunoglobulins (Igs) → antibodies

an IgG

antibodies mostly found in human whole blood

a fraction obtained from the plasma of a normal indiv

contains a variety of Abs specific for viral antigen

Inhibition of nucleic acid synthesis I

DNA is made up of a phosphate group, 5-carbon ribose sugar, nitrogenous

base

5’ cuz the last carbon from where the phosphate is attached is the 5’ carbon

antiparallel → strands run opposite of each other

5’ to 3’ pairs w 3’ to 5’

cuz of the base pairing

DNA elongation requires a free 3’ end

the OH group is where another phosphate group will attach

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 dapat free ung OH lagi para makapagbind ng another nucleotide

Acyclovir

a guanosine derivative selectively inhibits viral DNA polymerase

DNA polymerase

functions to promote bond formation on the joining units that

make up the backbone

sugar-phosphate backbone

if acyclovir binds to the backbone, the enzyme will not work, it

cannot bind to another phosphate group

stops DNA polymerase from joining units in the backbone

of the DNA

guanosine — the nitrogenous base is a guanine

replace guanosine in the DNA chain

no free OH in the 3’ end → stop the viral replication process

inhibit the enzyme acting on this portion

cannot add anymore another nucleotide for it to grow (not elongate)

counterfeit mechanism

enzymes are specific to a substrate

it has a stereochemical configuration that will bind to the

substrate

the drug is designed to look like the usual substrate, but if it binds
to DNA polymerase → no product

effective against Herpes virus (Type 1 & 2), Varicella-Zoster Virus (VZV)
→ chicken pox

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 Ganciclovir

a guanosine derivative is phosphorylated and then incorporated into

viral DNA suppressing its replication

used in cytomegalovirus infections

Inhibition of nucleic acid synthesis II

Vidarabine

an adenosine derivative, a selective inhibitor of viral DNA polymerase

analog of adenine

effective against Herpes simplex and Varicella Zoster

Ribavirin

similar to guanosine and is thought to interfere with the synthesis of

viral DNA

can inhibit much DNA and RNA virus

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 Inhibition of nucleic acid synthesis III

Foscarnet (NNRTI)

non-nucleoside reverse-transcriptase inhibitor (NNRTI)

direct inhibitor of DNA polymerase

inhibits viral DNA polymerase by attaching to the pyrophosphate

binding site

binding site in the phosphate group will be gone

Active against Herpes (I, II, Varicella, CMV) including those resistant to
Acyclovir and Ganciclovir

Zidovudine (NRTI)

nucleoside reverse-transcriptase inhibitors (NRTI)

the first type of drug available to treat HIV infection

act as a competitive inhibitor of reverse-transcriptase

prevents the conversion of RNA to DNA

an analog of thymidine

thymine

inhibits reverse transcriptase → effective against HIV

for HIV → monotherapy is ineffective cuz the virus mutates

so an AIDS cocktail is given

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 a cocktail of drugs

combination of a protease inhibitor, NNRTI, 2 NRTI, and a

booster drug

Zalcitabine and didanosine (NRTI)

reverse transcriptase inhibitors used in HIV infection

Neuraminidase inhibitor

Zanamivir and Oseltamivir

inhibits neuraminidase which is essential for virus replication

prevents the formation of viral aggregates and the spread of the virus

used against influenza A and B

they possess neuraminidase in their outer surface which is essential for

the release of virus particles from the infected cell

sialic acid is the usual substrate of neuraminidase

zanamivir and oseltamivir are analogs of sialic acid

instead of sialic acid binding to neuraminidase which will result in the

release of the virus, when zanamivir and oseltamivir are given, they will
bind to neuraminidase and there will be no release of the virus

immunomodulators

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 agents that modify our immune response or the functioning of the immune
system to make it stronger in fighting the virus

stimulate antibody formation

Interferons (INFs)c

pleomorphic cytokines

exhibits important biological activity — antiviral, antitumor,

immunomodulatory effect

inhibit viral mRNA

for Hepatitis B, Hepatitis C (INFs+Ribavirin), and AIDS

Palivizumab

a humanized monoclonal antibody, particularly IgG

produced by recombinant DNA technology

directed against the epitope, an antigenic site, particularly for Respiratory

Syncytial Virus (RSV)

Imiquimod

used topically to relieve and control genital and perianal warts caused
by viruses

-miquimod

used to treat skin conditions — face, scalp

certain types of skin cancer

superficial basal cell carcinoma

induce pro-inflammatory cytokines, chemokines, and other mediators that

could lead to the activation of antigen-presenting cells (cells that will
present the antigen to the antibody)

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