Virus proteins may have additional roles, some of which may be carried out by

structural proteins, and some by non-structural proteins (proteins synthesized by

the virus in an infected cell but they are not virion
components). These additional roles include
• enzymes, e.g. protease, reverse transcriptase
• transcription factors
• primers for nucleic acid replication
• interference with the immune response of the host.

Nomenclature of virus proteins

There is no standard system of nomenclature for virus proteins, with different systems having
evolved for different groups of viruses. For quite a number of viruses the following system has
been adopted, the proteins being numbered in decreasing
order of size:

• structural proteins VP1, VP2, VP3, . . . (VP =

virus protein)
• non-structural proteins: NSP1, NSP2, NSP3,
. . ..
Many virus proteins are known by an abbreviation
of one or two letters, which may indicate
• a structural characteristic G (glycoprotein)
P (phosphoprotein)
• or a function F (fusion)
P (polymerase)
RT (reverse transcriptase).
Overview of virus replication

The aim of a virus is to replicate itself, and in order to achieve this aim it needs to enter a host
cell, make copies of itself and get the new copies out of the cell. In
general the process of virus replication can be broken down into seven steps:

1. Attachment of a virion to a cell

2. Entry into the cell
3. Transcription of virus genes into messenger RNA
molecules (mRNAs)
4. Translation of virus mRNAs into virus proteins
5. Genome replication
6. Assembly of proteins and genomes into virions
7. Exit of the virions from the cell.

All animal viruses must cross the plasma membrane.

Some must cross the nuclear envelope, usually via a nuclear pore.
Some are transported in the cytoplasm via microtubules.
Replication of Phages
Incorrect Prophage Excision Creates Specialized Transducing Particles
GEnerAlized transduction
HIV

 There are two types of human immunodeficiency virus (HIV-1 and HIV-2), which each
evolved from a different simian immunodeficiency virus (SIV).

 Both viruses emerged in the late 20th century. In contrast to the SIVs, which appear not
to harm their natural primate hosts, HIV infection damages the immune system, leaving
the body susceptible to infection with a wide range of bacteria, viruses, fungi and
protozoa.

 This condition is called acquired immune deficiency syndrome (AIDS).

 HIV-1 is much more prevalent than HIV-2; it is HIV-1 that is largely responsible for the
AIDS pandemic, while HIV-2 is mainly restricted to West Africa.

 Now, in each year of the early 21st century there are approximately 5 million new HIV
infections, and approximately 3 million deaths from AIDS, which has become the fourth
biggest cause of mortality in the world.

 The magnitude of this problem has resulted in the allocation of huge resources to the
study of these viruses, major objectives being the development of anti-viral drugs and a
vaccine.

 The emphasis of this chapter is on HIV-1, as it has been studied more intensively than
HIV-2.
GENOME
REPLICATION

Attachment and entry

 The cell receptor for HIV-1 is CD4, which is found on several cell types, including helper
T cells and some macrophages; CD4 T cells are the main target cells.

 Attachment of the virion occurs when a site on gp120 recognizes a site on the outer
domain of CD4.

 As well as binding to receptor molecules anHIV-1 virion must also attach to a co-receptor
on the cell surface. The molecules that act as co-receptors have seven transmembrane
domains and are chemokine receptors.

 During immune responses they bind chemokines and these interactions control leukocyte
trafficking and T cell differentiation.
  The chemokine receptors are designated CCR and CXCR, respectively. A number of
these molecules on T cells act as coreceptors for HIV-1, particularly CCR5 and CXCR4

 The interaction of gp120 with the receptor and coreceptor results in a dramatic re-
arrangement of gp41, which proceeds to fuse the membranes of the virion and the cell.

 The contents of the virion envelope are released into the cytoplasm and develop into the
reverse transcription complex, which contains the MA, Vpr, RT and IN proteins, as well
as the virus genome.

REVERSE TRANSCRIPTION AND TRANSPORT TO THE NUCLEUS

RECOMBINATION

 Two RNA genomes are encapsidated in each HIV-1 particle.

 Upon infection and replication catalyzed by reverse transcriptase , recombination

between the two genomes can occur.

 Recombinatio occures as the single-strand (+) RNA genomes are reverse transcribed to
form DNA. During reverse transcription , the nascent DNA can switch multiple times
between the two copies of the viral RNA.

 S

 S

 s

ASSEMBLY AND EXIT OF VIRION

 Formation of the RNA dimer that will constitute the genome of a new virion commences
by base pairing between complementary sequences in the loop of the dimerization
initiation site near the 5_ end of each RNA.

 It is thought that this leads to the formation of a ‘kissing-loop complex’ that stabilizes
 the dimer.

 Molecules of Gag and Gag–Pol form an orderly arrangement, and their domains bind to
the virus genome and to other proteins that will become incorporated into the virion.

 S

 S

 s

PROGression / PATHOGENESIS of HIV INFECTION

 Shortly after a person becomes infected with HIV there is a huge rise in viraemia
(concentration of virus in the blood), and in some people there is an illness resembling
glandular fever or influenza.

 The host’s immune responses then control virus replication to some extent and there is a
period of asymptomatic infection.

 In the absence of intervention with drugs this period typically lasts for 8–10 years, but it
may be significantly shorter or longer than this, depending on characteristics of both the
host and the virus.

 Extensive virus replication continues throughout the asymptomatic period, with estimates
of more than 1010 HIV-1 virions produced each day.

 The infection persists in spite of immune responses against the virus and there are several
reasons for this.

 One reason is that the cell types killed by HIV infection (CD4 T cells and macrophages)
are those involved in the immune responses; there is also evidence that non-infected CD4
T cells are killed by apoptosis.

 CD4 T cells play pivotal roles as helpers for several cell types including B cells,
cytotoxic T cell precursors, natural killer cells and macrophages, hence immune
responses are impaired.

 Another reason why an HIV infection is not cleared is that the virus evolves as the
infection proceeds, producing new antigenic variants that may not be recognized by the
antibodies and T cells present.

 Furthermore, in latently infected cells the virus is shielded from the immune system.

 For a while, the body is able to tolerate the onslaught on the immune system by rapidly
replacing most of the cells that have been destroyed, but the concentration of CD4 T cells
in the blood steadily declines until a point is reached where the level of viraemia rises
sharply and AIDS develops.

 AIDS is characterized by infections with pathogenic micro-organisms; brain disease

and/or cancer may also develop. The most common types of cancer are those that are
associated with viruses, such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma.

 In comparison with HIV-1, HIV-2 infections are associated with longer asymptomatic
periods, slower progression of disease and lower rates of transmission.