LECTURE FIVE

5.0. LECTURE FIVE: BIOLOGY OF THE HIV VIRUS

5.1. Introduction

This lecture discusses the nature of viruses in general so that you are able to locate the HIV virus as a
biological agent. It then discusses the structure and life cycle of the HIV virus focusing on the important
features of what is a fairly simple biological unit, the role of each of these features and how the virus
makes new copies of itself in what is referred to as replication. This replication process occurs inside the
CD4 cells of the immune system eventually destroying them leading to a depletion of their numbers.
This is the underlying defect in a patient with HIV/AIDS.

5.2 Lecture Objectives

At the end of this unit you should be able to:

 Discuss the general characteristic of a virus including HIV and locate the place of the
HIV virus among other viruses
 Discuss the main structural features of the HIV virus
 Discuss the replication cycle of HIV virus and the role of each component of the virus
in that cycle.
 Briefly describe the effects of the HIV replication cycle on the immune system.

5.2. Biology of the HIV Virus

The Nature of Viruses

Viruses are the smallest microorganisms known to man. In spite of their minute size they have been of major
importance to man because of their ability to cause serious infections that have often appeared in epidemics.
Historically, viral diseases, a good example of which is small pox, were medical nightmares that used to result in
many deaths; until in this particular case, Edward Jenner the British Physician developed an effective vaccine against
it. More recently there is the flu epidemic of 1918 that is recorded as having caused millions of death. Then in the last
quarter of the twentieth Century the HIV virus emerged and it has had a devastating impact on the human population
which remains an ongoing challenge.
Viruses are obligatory (or obligate) parasites meaning that they only survive through the assistance of cells of a
suitable host. They do not have the resources such as mitochondria and ribosome which cells use to make their own
energy and proteins respectively. They therefore depend on the effort and resources of host cells to meet these
needs. In the case of the HIV virus the human being is the host and it is the CD4 cells of the human immune system
that play this role. Genetically, viruses have either Deoxyribonucleic Acid (DNA) or Ribonucleic Acid (RNA), with
most of the viruses including the HIV virus being in the latter category. The HIV virus is therefore identified as an
RNA virus.

5.3. The HIV Virus

The HIV virus is classified as a retrovirus a name derived from the way it replicates (makes copies of) itself; a
process which is discussed below. It is in the family of Lentiviruses”.Lenti” denotes “slowness” and the virus is so
called because it is slow in producing symptoms in infected people. There are two types of the virus- HIV Type 1 and
HIV Type 2.

HIV I is found worldwide and is the type that is responsible for the worldwide HIV pandemic. On the other hand HIV
type 2 is found mainly in West Africa, Mozambique and Angola. It is less aggressive, less efficiently transmissible
vertically ( mother –to- child) and the infection it causes has a slower progression.

The strains of HIV I, have three main groups classified as the Major group “M”, Outliers “O”, and the New or “N” – O
is present in a few areas in West Africa while N is rare. Therefore M is the most important group and has many
subtypes ( also known as ”clades”) of HIV ranging from A-K. A-E subtypes are the most important subtypes. There
are also small populations of what are called Circulating Recombinant Forms which are of mixed strains in origin

The next section will discuss the structure and life cycle of the HIV Virus.
5.4 The Structure of the HIV Virus

Diagram of the HIV virus

Source:https://www.niaid.nih.gov/diseases-conditions/hiv-replication-cycle

HIV is spherical in shape with a diameter of about 100nm which is approximately a millimeter divided
ten thousand times.

The Outer coat of the virus, known as the viral envelope is composed of two layers, of fatty molecules
(lipids) taken from the membrane of Human cell when a newly formed virus particle buds from the cells.

Embedded in the viral envelope are 72 copies on average of complex HIV protein that project from the
surface referred to as “spikes” or “studs”. This protein (spikes) consists of a cap made of 3 molecules of
glycoprotein (gp) 120 and a stem consisting of 3 gp 41 molecules that anchor the structure in the viral
envelope.

After the lipid layer there is a protein matrix layer- the P17 layer

The capsid (viral core or p24) surrounds two single strands of HIV RNA each of which has a copy of the
virus’ 9 genes. 3 of this contain information needed to make structural proteins that controls the ability of
HIV to infect a cell, produce new copies or virus or cause disease. The ends of each strand contain on
RNA sequence.
Enzymes:

The virus also has got several enzymes that help it to replicate. These include:

a) reverse transcriptase,

(b) integrase,

(c) protease.

The role of each of these enzymes in the replication cycle of the virus will be explained in the discussion
of the life cycle of the virus that comes next.
An Illustration of the events of the life cycle of the HIV virus courtesy of National Institute of
Infectious and Allergic Diseases at: https://www.niaid.nih.gov/diseases-conditions/hiv-replication-cycle.
5.5. Life Cycle of the HIV virus

HIV cannot reproduce itself outside a cell and when it invades a living cell, it turns it into a reproductive
machinery churning out as many copies of the virus before the cell dies.

Binding ( See diagrammatic illustration above)

Replication begins when a free HIV particle floating in the body fluid encounters a CD-4 cell. One of the
viruses GP 120 molecule binds to a CD-4 receptor and the Chemokine Co- receptors known as CCR5 and
CXCR4 .

Fusion and entry

This biding results in a conformational change in both the GP120 and GP 41 that leads to fusion of the
viral envelop and the CD4 cell membrane. This step is referred to as fusion.

Following fusion of the viral envelopes and cell membrane the viral core is able to gain entry into the
cytoplasm of the CD4 cell where host cell enzymes digest off the Capsid protein- P24. This frees the
Viral RNA and the viral enzymes to undergo the next step of replication.

Reverse Transcription

In the cytoplasm of the cell, a viral protein, reverse transcriptase enzyme converts single strands of R.N.A
into double stranded D.N.A (Deoxyribonucleic acid). This is the form in which the host cell has its
genetic material and by forming viral DNA the virus is preparing to get its genes reproduced as DNA has
the unique capacity of making copies of itself. This viral DNA is sometimes referred to as “Pre-
Integration Complex”.

Integration

This viral DNA is transported to the cell nucleus where it is spliced into the human D.N.A by the HIV
enzyme Integrase. Once integrated the HIV D.N.A is known as a pro-virus. The cell is unable to
distinguish viral D.N.A from its own genetic material. As the host cell DNA is copied so will the Viral
DNA. This gives the virus new genetic resources for the offspring viruses. The next steps look at how this
happens.

Transcription

For a pro-virus to produce new copies of the virus the viral DNA has to undergo a process of transcription
which involves the making RNA from the new copies of viral DNA made by the host cell. The process
results in an RNA strand and a messenger RNA (MRNA). The first is genetic material for the new viruses
while the second carries information that will help make viral proteins by the cell’s protein making
structures.

Translation
The messenger RNA is transported outside the nucleus, and is used as a blueprint for producing new HIV
proteins and enzymes. This process is called translation. In the cytoplasm the virus utilizes the host cells
protein making resources to make long chain viral proteins.

Assembly

The enzyme protease cleaves (breaks) the long chains of viral proteins into functional and structural
proteins. The host cell protein-building amino acids and RNA come together to facilitate production of
new viral protein. Newly made HIV core protein, enzymes and genomic RNA gather just inside the cell
membrane while the viral envelope proteins aggregate with the membrane.

Budding and Maturation

An immature viral particle forms and buds off from the cell, acquiring an envelope that includes both
cellular and HIV proteins from the cell membrane. The core of the virus is immature and the virus is not
yet infectious. Long chains of proteins and enzymes that make up the immature viral core are cleaved
into smaller pieces by protease enzymes. This results to an infectious virion particle.

5.6. Effects On Immunity Of The Host

The conversion of the body’s CD4 cells into virus manufacturing units result in rendering them
ineffective in their role as defenders of the body against infection. Subsequently, the CD4 cells are
destroyed by the process of manufacturing viruses or are targeted for destruction by other cells of the
immune system since they are carrying foreign antigens, the HIV virus. In time enough CD4 cells will be
destroyed leading to the body’s inability to protect itself against infections. The body will become more
and more vulnerable as the CD 4 cells are depleted, until the major illness of AIDS appear. Without
proper treatment these illness eventually kill the patient.
5.6. SUMMARY

This lecture has looked at the general characteristics of viruses and the various ways of
classifying them. It has also discussed the structure and replication cycle of the HIV virus
with a view to showing how this replication process eventually damages the immune
functions of the infected person.

NOTE

 Viruses are the smallest microorganism known and do not have a capacity to live
independently- they are obligatory parasites depending on other cells to survive and
multiply.
 The HIV virus depends on CD4 cells of the human body especially the T-lymphocytes
which it uses to make copies of itself weakening or destroying the cells in the process.
 It is the reduction in the number of CD4 cells in a person infected by the HIV virus that
Activities
results in immune deficiency.

Place an important point you want to emphasize here in your unit topics or subtopics.
ACTIVITY.

Access the internet and through the Google or Yahoo Search Engine search under the
topic “Theories of Origin of the HIV virus”. Read the various theories presented and
compare them for their merit. Which do you find most convincing?

Self-Test Questions

1. Give three general characteristics of viruses.

2. Discuss the structure of the HIV virus.

3. Discuss the replication cycle of the HIV virus showing the role of each viral component
involved in the process.
1.9 References.

Place here key references forming for this unit

REFERENCES.

1.Davidson’s Principals of Medicine, 1996 Edition

2.National Institute of Infectious and Allergic Diseases: https://www.niaid.nih.gov/diseases-

conditions/hiv-replication-cycle

3. National Training Curriculum on Antiretroviral Therapy, Ministry of Health Kenya.

4.Kenya AIDS Indicator Survey,2007.Ministry of Health Kenya

5.AIDS In The Workplace Policy Government of Kenya (DPM).2005

6.Wikipedia, Online encyclopedia.

7.Pratt R.,J.2003.HIV&AIDS A Foundation For Nursing and Healthcare Practice.London.Bookpower.

8.AMREF Community Health Manual.

9. UN /AIDS WEBSITE