Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Human immunodeficiency virus (HIV)

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Health. She became a trustee of Johns Hopkins University in

1992, and joined the council of the Johns Hopkins-Nanjing

University Center for Chinese and American Studies in 1993.

In addition to her duties as university administrator, scientist,

and mother, Huang is an avid reader of mystery novels, and

enjoys sailing.

See alsoViral genetics; Virology; Virus replication; Viruses

and responses to viral infection

HUMAN IMMUNODEFICIENCY VIRUS

(HIV)Human immunodeficiency virus (HIV)

The Human ImmunodeficiencyVirus (HIV) belongs to a class

of virusesknown as the retroviruses. These viruses are known

as RNAviruses because they have RNA as their basic genetic

material instead of DNA. The retroviruses are unable to repli-

cate outside of living host cells, because they contain only

RNA. However, they have the enzyme reverse transcriptase

that can make DNA from the RNA and allow them to integrate

into the host cell genome. The retroviruses are composed of

three subgroups, two of which are pathogenic to humans. They

are the oncarnovirus subgroup and the lentivirus (meaning,

slow virus) subgroup. The Human Immunodeficiency Virus,

which belongs to the lentivirus subgroup, is further divided

into two types based on the diseases they produce. The HIV-1

produces the acquired immunodeficiency syndrome (AIDS),

while the HIV-2 produces a similar disease that is at present,

largely restricted to West Africa.

The genetic material of the HIV virus consists of two

short strands of RNA about 9,200 nucleotides long, enclosed in

an outer lipid envelope. A viral glycoprotein (gp120) is dis-

played on the surface of the envelope. This protein recognizes

and binds to the CD4 receptor on T-helper cells. The HIV

genome contains a long terminal repeat (LTR) and the gag, pol,

env, and tax/rex genes. The LTR helps in the integration of the

virus into the host cell DNA. The gag genecodes for the pro-

teins that make up the outer core or capsid while the env gene

codes for the envelope glycoprotein including the outer enve-

lope glycoprotein (gp 120) and the transmembrane glycopro-

tein (gp141). The major proteins coded by the pol gene are the

reverse transcriptase, protease, and the integrase. The tax/rex

gene codes for certain factors that have a regulatory role.

The HIV infects cells that have the CD4 receptor mole-

cule on their surface. In macrophages and cells lacking this

molecule, an alternate receptor molecule (such as the Fc

receptor, or the complementreceptor site) may be used for

entry of HIV. The immune cells such as the blood monocytes,

macrophages, T cells, B cells, natural killer (NK) cells, den-

dritic cells, hematopoietic stem cells, etc are the primary tar-

gets of HIV infection.

After entering the body, the virus attaches itself by

fusion to a cell with the appropriate CD4 receptor molecule.

On gaining entry into the cell, the viral particle uncoats from

its envelope and releases the RNA. The reverse transcriptase

encoded by the pol gene, reverse transcribes the viral RNA

into DNA, and the integrase enzyme (also coded by the pol

gene) inserts the HIV proviral DNA into the genomic DNA of

the host cell. The HIV provirus is replicated by the host cell

and transcribed to produce new progeny RNA molecules. The

infected host cells either release the new HIV virions by lysis,

or the viruses can escape by surface budding. These go on to

infect additional host cells.

The primary target of the HIV is the immune system

itself, with a special affinity for CD4 (T-helper) cells.

Following infection, there is a latent phase during which the

viral replication continues actively, accompanied with a pro-

gressive destruction of the CD4 cells. During latency, there are

enough immune cells remaining to provide an immune

response and fight infections. Eventually, when a significant

number of T cells are destroyed, and the rate of production of

the cells cannot match the rate of destruction, there is a loss of

both cell-mediated and humoral immunity. This failure of the

immune system leads to the appearance of clinical AIDS. The

patients generally die of secondary causes such as Kaposi’s

sarcoma (a rare form of cancer that occurs in HIV-infected

individuals) or bacterial and fungal infections.

Primary HIV infection may go undetected in more than

half the cases, because the symptoms produced are mild and

they subside quickly. This is followed by a clinical latent

period, which could last on an average 8–11 years. The latency

period varies from person to person and depends on a variety

of factors including the person’s health status and life style. In

cases of acute HIV infection, the most common symptoms are

fever, swelling of the lymph glands, a red, diffuse rash all over

the body, sore throat or upper respiratory infection, muscle

ache, diarrhea, and headache. These symptoms subside in a

couple of months. Within three months of infection, the body

mounts an additional immune response to the virus, and

detectable levels of antibodies are seen. Both humoral and

cell-mediated immune responses play a role. There is a decline

in the viral counts and the levels of CD4 T-helper cells

increase. In rare cases, it may take as long as six months for

the immune response to develop. Therefore, the Centers for

Disease Control(CDC) recommends testing for HIV at six

Color enhanced scanning electron microscope image of the Human

Immunodeficiency Virus (HIV) on a hemocyte.

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