Viruses and Viral Infections

Mark Pallen
Nature of Viruses
 Virology - History
 Structure
 Classification
 Replication
 Pathogenesis
 Types of Infection
 Hazard Groups
 Periode awal
Anthony van Leeuwenhoek -- Periode modern
mikroscop
Louis Pasteur – fermentasi,swan regulasi gen
flask exp
Robert Koch – postulat koch rekombinan DNA
Periode penemuan virus
 Mayer ---TMV
onkology
 Ivanovsky & Beijerinck –contagiun
vivum fluidum vaksin
 Loffler & Frosch – virus hewan ,
penyakit kuku & mulut obat antiviral
 Twort & D’herelle -- bakteriofaga
 Origin of viruses : Unknown

 It is possible that the differences among DNA, RNA and utilized

RNA and DNA viruses are different origin.

 Two theories of viral origin:

1. Viruses may be derived from DNA or RNA nucleic acid

components of host cells that became able to replicate
autonomously.

2. Virus may be degenerate forms of intracellular parasites.

Origins of Virology
 1840 - Agents smaller  1948-55 - Cell Culture
than bacteria  1952 - Poliovirus
◦ “filterable viruses”  1969 - Hepatitis B
 1898 - Foot & mouth  1983 - HIV
 1901 - Yellow fever  1989 - HCV
 1903 - Rabies
 1933 - Influenza
Virus Structure
 Size
◦ 17 nm – 3000 nm diameter

 Basic shape
◦ Rod-like
◦ “Spherical”

 Protective Shell - Capsid

◦ Made of many identical protein subunits
◦ Symmetrically organized
◦ 50% of weight
◦ Enveloped or non-enveloped

 Genomic material
◦ DNA or RNA
◦ Single- or double-stranded
Viruses

Figure 13.1
Viruses should not be confused with
other infectious agents
 Chlamydia
 Mycoplasma
 Rickettsiae
 Bacteria
 Fungi
Differences between
bacteria and viruses
 Viruses  Bacteria
◦ Obligate intracellular ◦ Usually free-living, but can
parasites be parasites
◦ No ribosomes ◦ Ribosomes
◦ DNA or RNA, not both ◦ DNA and RNA
◦ seen by EM ◦ seen by LM
◦ 10-100s of genes ◦ 100s-1000s of genes
Principles of virology
Nomenklatur
tidak mengikuti penamaan binomial Linnaeus
 Taxonomy
orde akhiran virales
famili  akhiran viridae
subfamili akhiran virinae
genus  akhiran virus
spesies  tidak spesifik dapat lebih dari satu kata

family Herpesviridae, subfamily Betaherpesvirinae

genus Muromegalovirus
type species Murine herpesvirus 1
 Taksonomi orde Mononegvirales
Subfamili Genus Spesies
Famili
Bornaviridae Bornavirus Borna disease virus
Filoviridae Marburg-like viruses Marburg virus
Ebola-like-viruses Zaire Ebola virus

Paramyxoviridae Paramyxovirinae Respirovirus Sendal virus

Pneumovirinae Rubulavirus Mump virus
Morbilivirus Measles virus
Pneumovirus Human respiratory virus
Metapneunovirus Turkey rhinotracheis virus

Rhabdoviridae Vesiculovirus Vesicular stomatitis India virus

Lyssavirus Rabies virus
Ephemerovirus Bovine ephemeral fever virus
Novirhabdovirus Hematopoietic necrosis virus
Cytorhabdovirus Lettuce necrotic yellow virus
nucleorhabdovirus Potato yellow dwarf virus
 Viral Taxonomy
 Herpesviridae
◦ Herpesvirus
 Human herpes virus 1
 HHV 2
 HHV 3
 Retroviridae
◦ Lentivirus
 Human Immunodeficiency Virus 1
 HIV 2
The Baltimore classification system
Berdasarkan genetik dan pola replikasi virus.
Virus diklasifikasikan menjadi 7 kelas:

1. dsDNA viruses
2. ssDNA viruses
3. dsRNA viruses
4. (+) sense ssRNA viruses (codes
directly for protein)
5. (-) sense ssRNA viruses
6. RNA reverse transcribing viruses
7. DNA reverse transcribing viruses

"ds" = "double strand" and

"ss“ = "single strand".
 Asam nukleat
protein
Komposisi Kimia Virus
Lipid
Glikoprotein

Asam Nukleat
- Virus mengandung asam nukleat tunggal (RNA or
DNA) yang mengkode informasi genetik untuk
replikasi virus
- Ukuran genom virus DNA berkisar antara 3.2
kbp - 375 kbp.
- Ukuran genom virus RNA berkisar antara 7 kbp
- 30 kbp.
Protein
 Non-structural proteins—early phase
a. Regulators of viral gene expression
b. Enzymes for the viral replicative cycle
when virion enters a host cell.
c. Down regulation of host antiviral defenses.

Structural proteins—latest phase

a. Provide the structural symmetry of the virus particle.
b. Facilitate transfer of the virus nucleic acid from one cell to
another.
c. Protect the viral genome against inactivation by nucleases.
d. Determine the antigenic characteristics of the virus
 Viral lipid envelopes
- beberapa virus mempunyai envelope lipid sebagai bagian
dari struktur virus
- Lipid mempunyai fungsi pada saat nukleokapsid membentuk
pertunasan melalui membran sel dalam proses pematangan
- komposisi lipid bergantung pada tipe membran sel tempat
terjadinya proses pertunasan
- lipid Sensitif terhadap eter dan pelarut organik

Viral Glycoprotein
- Viral envelopes contain glycoproteins are virus encoded.
- Glycoproteins that attach the virus particle to a target
Structural Classes
•Icosahedral symmetry
•Helical symmetry
•Non enveloped (“naked”)
•Enveloped
Viral Structure
 Icosahedral capsids

a) Crystallographic structure of a b) The axes of symmetry

simple icosahedral virus.
Helical symmetry

In 1955, Fraenkel, Conrat,

and Williams
demonstrated that tobacco
mosaic virus (TMV)
spontaneously formed
when mixtures of purified
coat protein and its
genomic RNA were
incubated together.

TMV, a filamentous virus

Enveloped helical virus Enveloped icosahedral virus
 Growing Viruses

 Viruses must be
grown in living
cells.
 Bacteriophages
form plaques on a
lawn of bacteria.


Figure 13.6
 Growing Viruses

 Animal viruses
may be grown
in living
animals or in
embryonated
eggs.

Figure 13.7
 Growing Viruses
 Animal and plants viruses may be grown in
cell culture.
◦ Continuous cell lines may be maintained
indefinitely.

Figure 13.8
infection & replication of viruses

1. Attachment
2. Penetration
3. Uncoating
4. Transcription and/or
translation
5. Replication
6. Assembly
7. Release
Attach / Adsorpsi

 Adsorpsi virus pada host cell tergantung

pada interaksi antara
◦ nukleokapsid (naked virus)—membran host
cell
◦ Membran virus (enveloped virus)—membran
host cell
◦ Molekul spesifik—reseptor pada membran
host cell berbeda untuk setiap jenis virus
 bac
•Specific viral receptor
k
•Co-receptor
•Receptor-mediated endocytosis
•Fusion of the viral membrane at
the cell surface
Attach
Transkripsi, translasi, replikasi
 Replication of viruses
 Transcription - involves production
of mRNA
◦ RNA viruses use virus specified
enzymes
◦ DNA viruses use host cell enzymes
 Translation -Synthesis of viral
proteins & NA
◦ RNA viruses - viruses specified
polymerases
◦ DNA viruses - host cell
polymerases
 Assembly - nucleus, cytoplasm or
plasma membrane
 Release - cell lysis or budding through
plasma membrane
Sintesis mRNA virus
 Virus DNA  menggunakan RNA
polimerase host cell untuk membentuk
mRNA
 RNA virus umumnya memiliki RNA
polimerase
Translasi mRNA virus
 Translasi terjadi dalam sitoplasma
menggunakan ribosom host cell
 Pada fase awal  protein yang dihasilkan
adalah protein yang dibutuhkan untuk
replikasi asam nukleat virus
 Fase akhir dihasilkan protein untuk
kapsid
 Replikasi asam nukleat virus

 Selain harus menghasilkan molekul untuk pembentukan

kapsid baru, virus juga harus mereplikasi asam nukleatnya
 Replikasi virus DNA terjadi dalam nukleus host cell
 Kecuali poxvirus terjadi di sitoplasma
 DNA virus membentuk komplek dengan histon host cell
struktur yang stabil
 Pada herpes virus  mRNA di sitoplasma ditranslasi
menjadi DNA polimerase  sintesis DNA virus baru
 Adenovirus menggunakan enzim virus dan enzim host
untuk replikasi DNA
Perakitan & pelepasan virion

 Perakitan dari asam nukleat virus dengan

kapsomer yang disintesis akan membentuk
nukleokapsid dapat terjadi di sitoplasma atau
dalam nukleus host
 Virus envelope
protein envelope dan glikoprotein yang telah
ditranslasi dari mRNA virus diinsersikan ke area
membran plasma host
virus baru mengambil membran plus molekul
virus sebagai envelope
Perakitan & pelepasan virion
 Formation of the viral envelope

Insertion of
glycoproteins
into the cell’s
membrane
structures
Resume—Sifat umum Virus
 bahan genetik virus terdiri dari DNA atau RNA ,
tetapi tidak terdiri dari dua asam nukleat tersebut
 struktur virus sangat sederhana, terdiri dari
pembungkus yang mengelilingi asam nukleat
 virus bereproduksi hanya dalam sel hidup
 virus tidak membelah diri dengan pembelahan biner
 asam nukleat virus yang menginfeksi sel mengambil
alih sistem sel hospesnya sehingga selaras dengan
sintesis asam nukleat dan protein virus
  komponen virus dibentuk terpisah kemudian
dirakit sebelum dibebaskan
 pada proses pembebasan virus tertentu
memperoleh envelope dari membran sel
hospes

partikel virus yang lengkap—virion terdiri dari asam

nukleat dikelilingi oleh protein antigenik—kapsid
dengan atau tanpa selubung—envelope
 Perkembangan virus hanya terjadi dalam sel hidup
 Untuk tujuan replikasi virus host cell menyediakan
sistem untuk sintesis protein & asam nukleat virus
 Komponen virus hasil sintesis dalam host cell
bergabung membentuk virion infeksius baru
 Jumlah virion per sel bervariasi hingga > 100,000
partikel
 Lama siklus replikasi virus dalam sel juga sangat
bervariasi 6-8 jam (picornavirus)—lebih dari 40 jam
(herpesvirus)
 Reaction to Physical and Chemical Reagents

 Radiation: Ultraviolet, X-ray, and high-energy particles inactivate

viruses.

 Ether: Disrupts viral membrane.

 Detergents: Solubilize viral envelopes and disrupts capsids into

separated proteins.

 Formaldehyde: Reacts with nucleic acid and destroys viral

infectivity.

 Antibiotics: No effect on viruses.