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JKUAT SODeL 2013 JJ II J I J Doc Doc I Back Close JOMO KENYATTA UNIVERSITY OF AGRICULTURE & TECHNOLOGY SCHOOL OF OPEN, DISTANCE AND eLEARNING P.O. Box 62000, 00200 Nairobi, Kenya E-mail: [email protected] SZL 2111: HIV/AIDs LAST REVISION ON May 10, 2013

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JOMO KENYATTA UNIVERSITY

OF

AGRICULTURE & TECHNOLOGY

SCHOOL OF OPEN, DISTANCE AND eLEARNING

P.O. Box 62000, 00200

Nairobi, Kenya

E-mail: [email protected]

SZL 2111: HIV/AIDs

LAST REVISION ON May 10, 2013

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This presentation is intended to covered within one week.

The notes, examples and exercises should be supple-

mented with a good textbook. Most of the exercises have

solutions/answers appearing elsewhere and accessible by

clicking the green Exercise tag. To move back to the same

page click the same tag appearing at the end of the solu-

tion/answer.

Errors and omissions in these notes are entirely the re-

sponsibility of the author who should only be contacted

through the Department of Curricula & Delivery

(SODeL) and suggested corrections may be e-mailed to

[email protected].

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SZL 2111 HIV/AIDs

LESSON 4

Biology of HIV

Learning outcomes

By the end of this topic you should be able to;

� To know the nature of HIV

� Describe the structure of HIV

� Understand the Life cycle of HIV

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4.1. Nature of HIV

HIV can’t grow or reproduce on its own. It requires cell of

living organisms to infect & reproduce. HIV is specific to CD4+

cells in the human body i.e. cells with surface molecule called

Cluster of Differentiation 4. Cells carrying this molecule are

called CD4+ cells. Therefore HIV cant survive in the animal

blood, because its only human blood that contains CD4+cells.

HIV is a lentivirus. Like all viruses in this group it attacks the

immune system. Lentiviruses are in turn part of a larger group of

viruses called retroviruses. The term ”retrovirus” stems from the

fact that these kinds of viruses are capable of copying RNA into

DNA. The name lentivirus means slow virus. This is because

they take such a longtime to produce any adverse effects in the

body.

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SZL 2111 HIV/AIDs

4.2. The Structure of HIV

Outside of a human cell, HIV exists as roughly spherical par-

ticles (sometimes called virions). The surface of each particle

is studded with lots of little spikes. An HIV particle is around

100-150 billionths of a meter in diameter. That’s about the same

as 0.1 microns or 4 millionths of an inch or one seventieth of the

diameter of a human CD4+ white blood cell. Unlike most bac-

teria, HIV particles are much too small to be seen through an

ordinary microscope. However they can be seen clearly with an

electron microscope.

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NB: The proteins gp120 and gp41 together make up the

spikes that project from HIV particles, while p17 forms the ma-

trix and p24 forms the core.

Structurally HIV consist of

1. The viral envelope - HIV has a diameter of 1/10,000 of

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a millimeter and is spherical in shape. The outer coat of

the virus, known as the viral envelope, is composed of two

layers of fatty molecules called lipids, taken from the mem-

brane of a human cell when a newly formed virus particle

buds from the cell. Embedded in the viral envelope are

proteins from the host cell as well as 72 copies (on aver-

age) of a complex HIV protein (frequently called ”spikes”)

that protrudes through the surface of the virus particle

(virion). This protein, known as Env, consists of a cap

made of three molecules called glycoprotein (gp) 120, and

a stem consisting of three gp41 molecules that anchor the

structure in the viral envelope. Much of the research to de-

velop a vaccine against HIV has focused on these envelope

proteins.

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2. Viral core/capsid - The viral core (or capsid) is usually

bullet-shaped and is made from the protein P24. The core

contains:

(a) Two copies of identical strands of RNA - HIVs’ ge-

netic material

i. Almost all organisms, including most viruses, store

their genetic material on long strands of DNA.

ii. Retroviruses are the exception because their genes

are composed of RNA (Ribonucleic Acid).

iii. RNA has a very similar structure to DNA. How-

ever, small differences between the two molecules

mean that HIV’s replication process is a bit more

complicated than that of most other viruses.

(b) Three viral enzymes: required for HIV replication

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� Reverse transcriptase (RT)- converts viral RNA

to ds DNA

� Integrase- integrates DNA produced by RT into

human DNA

� Protease/proteinase- cuts proteins into segments

& facilitates assemblance of new viral copies.

3. Matrix - Just below the viral envelope is a layer called

the matrix, which is made from the protein p17 which

maintains the integrity of the virus structure & transport

genetic material.

4. Double layered lipid envelope -

� HIV particles surround themselves with a coat of fatty

material known as the viral envelope (or membrane).

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� Projecting from this are around 72 little spikes, which

are formed from the proteins gp120 which protrudes

from the surface & binds CD4+ cells and gp41. which

is embedded within the envelope & is for entry/fusion.

4.3. The Life Cycle of HIV/ HIV Replication

1. Attachment - The gp120 on the surface of the virus par-

ticle bind to the CD4 receptor on the surface of human

T cell and the viral envelope fuses with the human T cell

membrane.

2. Entry - The contents of the HIV particle are then released

into the cell, leaving the envelope behind.

3. Reverse Transcription - Once inside the cell, the HIV

enzyme reverse transciptase converts the viral RNA into

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DNA, which is compatible with human genetic material(DNA)

4. Integration - This DNA is transported to the cell’s nu-

cleus, where it is spliced into the human DNA by the

HIV enzyme integrase. Once integrated, the HIV DNA

is known as provirus.

5. Transcription - HIV provirus may lie dormant within a

cell for a long time. But when the cell becomes activated, it

treats HIV genes in the same way as human genes. First

it converts them into messenger RNA (using human en-

zymes).

6. Translation - Then the messenger RNA is transported

outside the nucleus, and is used as a blueprint for produc-

ing new HIV proteins and enzymes.

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7. Assembly & Budding - Among the strands of messenger

RNA produced by the cell are complete copies of HIV ge-

netic material. These gather together with newly made

HIV proteins and enzymes to form new viral particles,

which are then released from the cell. The enzyme pro-

tease plays a vital role at this stage of HIV’s life cycle by

chopping up long strands of protein into smaller pieces,

which are used to construct mature viral cores.

8. Maturation & release - The newly matured HIV parti-

cles are ready to infect another cell and begin the replica-

tion process all over again. In this way the virus quickly

spreads through the human body. And once a person is

infected, they can pass HIV on to others in their bodily

fluids.

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Exercise 1. � Revision Questions

Discuss the life cycle of HIV.

Example �. Are there other ways to avoid getting HIV through

sex?

Solution: The male condom is the only widely available barrier

against sexual transmission of HIV. Female condoms are fairly

unpopular in the U.S. and still relatively expensive, but they

are gaining acceptance in some developing countries. Efforts are

also under way to develop topical creams or gels called ”microbi-

cides,” which could be applied prior to sexual intercourse to kill

HIV and prevent other STIs that facilitate HIV infection. �

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Revision questions or guidelines

1. “The knowledge of HIV life cycle has advanced the fight

against HIV through designing of antiretroviral drugs”.

Using appropriate examples, discuss this statement.

2. Control of HIV/AIDs is directly linked to the knowledge of

the transmission of the causative agent. Discuss in detail

this statement.

3. The use of antiretroviral drugs is facing various challenges.

Highlight and briefly discuss the major limitation to the

use of ARVs.

4. Anything else you would like to suggest

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References and Additional Reading Materials

1. Maranga R. O, Muya S. M and Ogila K. O (2008) Funda-

mentals of HIV/AIDS Education. Signon Publishers.

2. Barry D. S. (1999) AIDS and HIV in Perspectives. CPU.

ISBN-13: 9780521627665

3. Ellison G. Parker M., Camphpbell C (2003) Learning from

HIV and AIDS. Cambridge CPU.ISBN-13: 9780521709286.

4. Shavitri Ramaiah (2008) HIV/AIDS; Health solutions. Ster-

ling Publishers Ltd. ISBN-9788120733305.

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Solutions to Exercises

Exercise 1. Entry in the CD4 + - Binding of GP 120 to CD

molecule allows it to bind to co-receptor causing fusion of viral

and cell membrane leading to entry of virus into cell. Reverse

transcription - Conversion of viral RNA into viral DNA under

the influence of reverse transcriptase in the cytoplasm. Integra-

tion - Viral DNA moved into cell nucleus where it is integrated

with host cell chromosome under the influence of intergrase.

Transcription - Production of new viral mRNA molecules for

production of viral RNA involving host cell enzymes. Transla-

tion - Viral mRNA is transported to the cytoplasm to produce

viral structural proteins under the influence of HIV Proteins.

Assembly and budding - Newly made HIV core proteins en-

zymes and genome RNA gather inside cell and they bud off.

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Maturation - The core of the virus is immature and therefore

un-infectious protease breaks the long protein chains causing vi-

ral particles.

Exercise 1

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