EGERTON UNIVERSITY

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E-CAMPUS

ZOOL 143: Biology of HIV/AIDS and Society

Topic 4 Handout

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Topic Four: Basic Biology of the HIV Particle

Introduction

In our first topic, we learned that HIV infection can cause immunodeficiency
disease called HIV/AIDS. In this topic we discuss the nature of HIV particle in
terms of its structure, characteristics, genetics, classification as well as its origin
and distribution.

Learning Outcomes

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

i. Describe the structure and characteristics of HIV particle

ii. Explain the classification of HIV particle.
iii. Explain the origin and global distribution of HIV strains.

4.1 Nature of Viruses

a) General Concepts on Viruses

Viruses contribute significantly to the global burden of infectious diseases. Most

of the diseases are mild, but viruses may cause severe diseases in susceptible
individuals, such as the malnourished, immuno-compromised, the very old and the
very young.

Viruses are simple acellular entities consisting of one or more of either DNA or
RNA enclosed in a shell of protein. Viruses are very small, sizes range 20 - 200
nm, beyond the resolving power of the light microscope. Viruses are
metabolically inert and can only replicate inside a host cell. Infectious virus
particle is called virion. Protein shell which surrounds and protects the genome is
called capsid. It is built up of multiple (identical) protein sub-units called
capsomers. Capsids are either icosahedral or tubular in shape. The genome
together witht the capsid is called Nucleocapsid.

There are four exceptions to the typical virus as described previously:

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 • Defective viruses- Composed of viral nucleic acid and proteins, but
cannot replicate without a helper virus.
• Pseudoviruses- Contain host DNA instead of viral DNA.
• Viriods- Consist of a single molecule of circular RNA with no protein
coat or envelope.
• Prions - Are the smallest known infectious particles.

Viruses occur in two phases:

• Extracellular phase – occur as a particle (a virion); cann’t multiply

outside a cell.
• Intracellular phase – occur as replicating nucleic acids, and synthesize
virion components.

b) Classification of Viruses

Viruses are mainly classified by phenotypic characteristics, such as morphology,

nucleic acid type, mode of replication, host organisms, and the type of disease
they cause. Helical morphology is seen in many filamentous viruses while
spherical viruses are characterized by Icosahedral morphology. Many viruses also
have an outer membrane envelope. The Baltimore classification (Figure 3.1),
developed by David Baltimore, is a virus classification system that groups viruses
into seven classes depending on their type of genome and their method of
replication:

• Class I: dsDNA viruses (e.g. Adenoviruses, Herpesviruses, Poxviruses)

• Class II: ssDNA viruses (+ strandDNA) (e.g. Parvoviruses)

• Class III: dsRNA viruses (e.g. Reoviruses)

• Class IV: (+)ssRNA viruses (sense RNA strand, e.g. Picornaviruses,

Togaviruses)

• Class V: (−)ssRNA viruses (antisense RNA strand, e.g. Orthomyxoviruses,

Rhabdoviruses)

• Class VI: ssRNA-RT viruses (+ RNA strand with DNA intermediate in

life-cycle (e.g. Retroviruses such as HIV)

• VII: dsDNA-RT viruses (e.g. Hepadnaviruses)

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Figure 4.1: The Baltimore classification of viruses (Source: Wikipedia)

4.2 Description of HIV Particle

a) Characteristics of HIV Particle

Human immunodeficiency virus (HIV) is a retrovirus, a positive (+) sense single

stranded RNA virus. It replicates through a DNA intermediate by use of reverse
transcriptase to convert the positive sense RNA into DNA. During infection, it
integrates its DNA into host genome. It is a membrane-enveloped retrovirus and
known to mutate faster than any other virus known to man.

b) Structure of HIV Particle

HIV particles surround themselves with a coat of fatty material known as the viral
envelope (or membrane) (Figure 4.2). Projecting from its surface are about 72
little spikes, which are formed from the glycoprotein 120 (gp120) and gp41. Just
below the viral envelope is a layer called the matrix, which is made from the
protein p17. The viral core (or capsid) is usually bullet-shaped and is made from
the protein p24. Inside the core are three enzymes required for HIV replication

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called reverse transcriptase, integrase and protease. Also held within the core are
two copies of ssRNA.

Figure 4.2: Anatomy of HIV particle (Source: virology.uct.ca.za)

c) The HIV Genome

HIV genome has nine genes (compared to more than 500 genes in a bacterium).
These genes are grouped as either structural genes or regulatory genes (Figure
4.3). Structural genes contain information needed to make structural proteins for
new virus particles while regulatory genes code for proteins that control the ability
of HIV to infect a cell, produce new copies of virus, or cause disease. At either
end of the ssRNA is a long terminal repeat sequence (LTR), which helps to
control HIV replication.

i) Structural genes

• gag gene – encode for core and shell of virus;

• pol gene – code for viral enzymes: reverse transcriptase, integrase and
protease
• env gene – code for envelope glycoproteins gp120 and gp 41

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ii) Regulatory genes

• vif gene – influences infectivity of viral particle;

• vpr gene – stimulates promoter region;
• vpu gene (in HIV-1 only) and vpx gene (in HVI-2 only) - enhances
maturation and release of hiv virions from cells;
• tat gene- have stimulatory effect on synthesis of all viral proteins;
• rev gene – required for expression of structural genes;
• nef gene – down regulates viral replication (e.g. during latency stage)

Figure 4.3: The HIV genome (Adapted from: Hoffmann and Rockstroh, 2012;
Battacharya and Sinha, 2006)

d) Classification of HIV Particle

HIV is classified as follows:

• Class - Class VI viruses single stranded RNA virusesthat replicate

through a DNA intermediate.
• Family - Retroviridae (Retroviruses)
• Genus – Lentiviridae (Retroviruses); cause diseases with long incubation
period.
• Types – HIV -1 and HIV-2
• Groups:
• Subtypes:

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e) HIV Types, Groups and Subtypes

HIV is a highly variable virus which mutates very readily; hence there are many
different strains of HIV, even within the body of a single infected person. Based
on genetic similarities, the numerous virus strains may be classified into types,
groups and subtypes. There are two types of HIV: HIV-1 and HIV-2. Each HIV
type is divided into groups, and each group is divided into subtypes and CRFs
(Figure 4.3). The strains of HIV-1 can be classified into four groups on the basis
of differences in env gene and their SIV origin:

• Group M ‘major’- originated from Chimpanzee

• Group N ‘new’ – originated from chimpanzee
• Group O ‘outlier’ – origin not known
• Group P ‘putative’ – originated from western gorilla

These four groups may represent four separate introductions of simian

immunodeficiency virus into humans.

Figure 4.3: HIV groups and subtypes (Source: Noble, 2009)

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Figure 4.4: Phylogenetic tree of HIV-1 groups and subtypes (Source: Vallari et
al., 2011)

4.3 Origin and Distribution of HIV Strains

a) Origin of HIV

HIV particle was first widely recognized in 1981, although evidence of the virus
was found in stored blood collected in 1959, and so it seems that it has been in
existence for longer than was first thought. Both HIV-1 and HIV-2 are believed
to have originated in West-Central Africa and jumped species (zoonosis) from a
non-human primate to humans in the twentieth century.

HIV evolved from a Simian Immunodeficiency Virus (SIV) which naturally

occurs in Old World primates, particularly Common Chimpanzees (Pan
troglodytes troglodytes), Sooty Mangabey monkeys (Cercocebusatys), De
Brazza's guenon (Cercopithecus neglectus), mandrill (Mandrillus sphinx) and
gorilla (Gorilla gorilla), are naturally infected with SIV. SIV exhibits a somewhat
different behaviour in its natural hosts; evokes only a mild immune response, does
not develop into simian AIDS, and does not undergo the extensive mutation and
recombination typical of HIV.

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HIV-1 originated in southern Cameroon after jumping from wild Common
Chimpanzees to humans, with exception of group P which originated from gorilla
in western Cameroon. HIV-2, on the other hand originated from the Sooty
Mangabey, an Old-World monkey of Guinea-Bissau, Gabon, and Cameroon.

b) Global Distribution of HIV Strains

i) HIV-2

The relatively uncommon HIV-2 is concentrated in West Africa (Cape Verde,

Gambia, Guinea Bissau, Guinea Conakry, Senegal, Sierra Leone and Mauritania).
HIV-2 is less easily transmitted, and the period between initial infection and
illness is longer. HIV-2 is strictly more like certain types of simian
immunodeficiency virus (SIV) than it is like HIV-1. Both HIV-2 and SIV carry an
extra gene not found in HIV-1, which encodes viral protein X.

ii) HIV-1

Worldwide, the predominant virus is HIV-1, and generally when people refer to
HIV without specifying the type of virus, they will be referring to HIV-1. HIV-1
is more pathogenic than HIV-2. The reason seems simply that once it's integrated
into a cell, it is faster at producing new virus particles. Group O appears to be
restricted to west-Central Africa while group N and Pare extremely rare. Group M
is most prevalent and is responsible for more than 90% of HIV-1 infections.

Within group M the most prevalent are subtypes B (found mainly in North
America and Europe), A and D (found mainly in Africa), and C (found mainly in
Africa and Asia). Subtype E is found in Thailand, Japan and India. Occasionally,
two viruses of different subtypes can meet in the cell of an infected person and
form a hybrid known as "circulating recombinant forms" or CRFs. For
example, the CRF A/B is a mixture of subtypes A and B.

Topic Summary

We have learned that:

• Human immunodeficiency virus (HIV) is an ssRNA virus surrounded with

a lipid membrane containing 72 glycoprotein spikes. The viral core is
usually bullet-shaped and encloses two copies of ssRNA and three

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 enzymes. HIV genome has just nine genes grouped as either structural or
regulatory genes.
• Both HIV-1 and HIV-2 are believed to have originated in West-Central
Africa through zoonosis from a non-human primate: Common
Chimpanzees of Cameroon and Old-World monkey of Guinea-Bissau,
Gabon, and Cameroon, respectively.
• HIV-2 is concentrated in West Africa, is less easily transmitted, and have
very long latency period. HIV-1 is spread worldwide and is more
pathogenic than HIV-2. Group M of HIV-1 is most prevalent and is
responsible for more than 90% of HIV-1 infections. Within group M the
most prevalent are subtypes B (found in North America and Europe), A and
D (found in Africa), and C (found in Africa and Asia).

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