Comparative Virology Retroviruses Slides

Comparative virology
Dr. N. Opoku

Reverse Transcribing Viruses:- Retroviruses
and ds-DNA RT viruses
Retroviruses
• large and diverse family of enveloped RNA viruses
• Normally single-stranded positive-sense RNA virus
• Outer lipid envelope incorporates and displays the viral glycoproteins

Schematic cross section through a retroviral particle.
Envelope consist of transmembrane (TM) and the surface (SU) components linked together by disulfide bonds.
Internal nonglycosylated structural proteins which are the matrix (MA) protein, capsid (CA) protein, and nucleocapsid (NC)
protein. Also contains transcriptase (RT), integrase (IN) and protease (PR)

•The virion RNA is 7–12 kb in size,
•it is linear
•single-stranded
•Non-segmented
•positive polarity
The hallmark of the family is its replicative strategy
That is reverse transcription of the virion RNA into
linear double-stranded DNA and the subsequent
integration of this DNA into the genome of the cell.

• Retroviruses are broadly divided into two categories—simple and
complex—distinguishable by the organization of their genomes
All retroviruses contain three major coding domains with information
for virion proteins:
 gag, which directs the synthesis of internal virion proteins that form
the matrix, the capsid, and the nucleoprotein structures;
pol, which contains the information for the reverse transcriptase and
integrase enzymes;
and env, from which are derived the surface and transmembrane
components of the viral envelope protein.
 An additional, smaller, coding domain present in all retroviruses
is pro, which encodes the virion protease
Retroviruses with this basic coding regions are known as Simple
retroviruses
• Complex retroviruses code for additional regulatory nonvirion proteins

A) A simple retroviral genome with the four major coding regions, gag, pro, pol, and env. Different reading frames are indicated
by vertical displacement of the coding region. The pro gene is encoded in the gag reading frame. The terminal noncoding
sequences include two direct repeats (R), a U5 (5′unique), and a U3 (3′unique) sequence. (B) A complex retroviral genome,
besides the major coding domains, information for two regulatory proteins, Tax and Rex, encoded in regions (boxes) joined by
RNA splicing. In this case, gag, pro, and pol are all in different reading frames.

• Retroviruses are further subdivided into seven groups defined by
evolutionary relatedness
• Five of these groups represent retroviruses with oncogenic potential
(formerly referred to as oncoviruses),
• and the other two groups are the lentiviruses and the spumaviruses.
• All oncogenic members except the human T-cell leukemia virus–
bovine leukemia virus (HTLV-BLV) genus are simple retroviruses.
HTLV-BLV and the lentiviruses and spumaviruses are complex.

Classification of retroviruses
Genus Example Virion morphology Genome
1. Avian sarcoma and
leukosis viral group
Rous sarcoma virus central, spherical core “C
particles”
simple
2. Mammalian B-type viral
group
mouse mammary tumor
virus
eccentric, spherical core
“B particles”
simple
3. Murine leukemia-related
viral group
Moloney murine
leukemia virus
central, spherical core “C
particles”
simple
4. Human T-cell leukemia–
bovine leukemia viral
human T-cell leukemia
virus
central, spherical core complex
5. D-type viral group Mason-Pfizer monkey
virus
cylindrical core “D
particles”
simple
6. Lentiviruses human
immunodeficiency virus
cone-shaped core complex
7. Spumaviruses human foamy virus central, spherical core complex

• Oncogenic retroviruses occur in all classes of vertebrates, and many
act as natural carcinogens.
• Some of the best studied are Rous sarcoma virus (RSV), a highly
pathogenic agent inducing connective tissue tumors in chickens;
mouse mammary tumor and murine leukemia viruses (MMTV and
MLV), more recently HTLV
• The lentiviruses are also found ubiquitously, causing disease
principally by killing or inducing loss of function of specific cells and
tissues.
• A representative example is human immunodeficiency virus (HIV), the
causative agent of acquired immunodeficiency syndrome (AIDS).

Multiplication of retro viruses
• There are seven steps in the replication cycle of the retrovirus.
1.is attachment, in which the retrovirus uses one of its glycoproteins
to bind to one or more specific cell-surface receptors on the host cell.
Steps 2 and 3 are penetration and uncoating, respectively.
Retroviruses penetrate the host cell by direct fusion of the virion
envelope with the plasma membrane of the host. Continuation of this
fusion process results in the release of the viral capsid directly into
the host cell's cytoplasm, where it is partially disrupted.
4. is replication, which occurs after the retrovirus has undergone
partial uncoating.
• At this stage, the RNA genome is converted by reverse transcriptase
into double-stranded DNA.

• Reverse transcriptase has three enzymatic activities:
RNA-directed DNA polymerase makes one DNA strand,
DNA-directed DNA polymerase makes the complementary strand,
and RNAse H degrades the viral RNA strand.
This results synthesis of a double-stranded copy of the retroviral genome
that is termed the "provirus," or proviral DNA.
This proviral DNA transported to the host cell's nucleus,
it is integrated, apparently at random, into the genome by means of the
retroviral enzyme called integrase.
Following integration, the provirus behaves like a set of cellular genes and
begin transcription back into mRNA.
 This transcription is carried out by RNA polymerases in the host cell.
Transcription of the proviral DNA is also the means of generating progeny
RNA. Viral proteins are made in the cytoplasm of the host cell by cellular
ribosomes.

5 is assembly," in which retrovirus capsids are assembled in an
immature form at various locations in the host cell.
6. an "egress" stage, in which the envelope proteins of
retroviruses are acquired by budding from the plasma
membrane (cell surface) of the host.
 Finally, step 7 is "maturation." In this step, the Gag and Pol
proteins of the retrovirus are cleaved by the retroviral protease,
thus forming the mature and infectious form of the virus.

• When retroviruses have integrated their own genome into the germ
line, their genome is passed on to a following generation.
• These endogenous retroviruses (ERVs), are known to make up 5-8% of
the human genome.
• Most insertions have no known function and are often referred to as
"junk DNA".
• However, many endogenous retroviruses play important roles in host
biology, such as control of gene transcription, cell fusion during
placental development in the course of the germination of an
embryo, and resistance to exogenous retroviral infection

Sub viral pathogens
 Viroids
small "naked" infectious RNA molecules that are pathogens of higher
plants
Viroids consist solely of short strands of circular, single-
stranded RNA without protein coats
Characteristics of Viriods
I. Small circular RNA molecules
II. Do not code for any protein
III. Not vector transmitted
IV. Can replicate autonomously

 Satellites
Small RNA molecules but depend on helper-virus for infection and
replication
Considered as parasites of parasites
Have the ability to suppress or enhance disease symptoms
Mostly have linear RNA
Some may have circular RNA like viroids, these are known as
virusoids

Prions
• A prion is an infectious agent composed entirely
of protein material, called PrP (short for prion protein)
• can fold in multiple, structurally distinct ways, at least one of
which is transmissible to other prion proteins, leading
to disease that is similar to viral infection.
• They are suspected to be the cause of transmissible spongiform
encephalopathies (TSEs) among other diseases.
• Good article at https://en.wikipedia.org/wiki/Prion

Comparative Virology Retroviruses Slides

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