How HIV destroys CD4 T cells !

Process

HIV enters and destroys the helper T cells that coordinate immunity. As their number falls, germs that are harmless to healthy people cause disease.

Updated 2026-11-01

What it is

HIV is a retrovirus that infects cells carrying CD4 together with a chemokine co-receptor (CCR5 or CXCR4): mainly helper T cells, macrophages and dendritic cells. It copies its RNA into DNA, inserts it into the host genome and persists as a latent reservoir. Over years, direct killing, inflammatory cell death and chronic immune activation deplete CD4 T cells until the immune system can no longer control opportunistic infections and some cancers (AIDS). The CD4 count predicts which infections are likely.

Key facts

The viral reservoir of latent provirus in resting memory CD4 cells is why antiretroviral therapy controls HIV but does not cure it.
People homozygous for the CCR5-Δ32 deletion are highly resistant to CCR5-using strains.
Loss of gut CD4 cells weakens the mucosal barrier; microbial products leaking into the blood drive chronic immune activation.
The CD4/CD8 ratio inverts; B cells are activated non-specifically, so immunoglobulins rise even though specific responses are poor.
With effective antiretroviral therapy the viral load becomes undetectable, CD4 counts recover and the virus is not transmitted sexually.

Step by step

The envelope protein gp120 binds CD4, then a co-receptor: CCR5 (strains transmitted between people) or CXCR4 (strains that often appear later).
gp41 fuses the viral and cell membranes; the viral core enters the cytoplasm.
Reverse transcriptase copies viral RNA into DNA with many errors, so the virus mutates fast and escapes antibodies and T cells.
Integrase inserts the viral DNA into a host chromosome (provirus); in resting memory CD4 cells it can stay silent for years.
Acute infection: very high viraemia and massive loss of memory CD4 cells in gut lymphoid tissue; often a flu-like illness.
CD8 T cells and antibodies lower the viral load to a set point, but do not clear the virus (clinical latency).
CD4 cells keep falling through viral killing, pyroptosis of abortively infected cells, CTL killing and chronic immune activation.
Below about 200 CD4 cells per microlitre (or with an AIDS-defining illness) the person has AIDS: opportunistic infections and cancers appear.

CD4 count and typical opportunistic infections (cells per microlitre; tuberculosis can occur at any count)

CD4 count	Typical infections and cancers	Organism
Any count, more frequent below 500	Tuberculosis, oral candidiasis, herpes zoster, bacterial pneumonia, Kaposi sarcoma	M. tuberculosis, Candida, varicella-zoster virus, pneumococcus, HHV-8
Below 200	Pneumocystis pneumonia	Pneumocystis jirovecii
Below 150	Disseminated histoplasmosis (common in Latin America)	Histoplasma capsulatum
Below 100	Toxoplasma encephalitis, cryptococcal meningitis, oesophageal candidiasis	Toxoplasma gondii, Cryptococcus neoformans, Candida
Below 50	Cytomegalovirus retinitis, disseminated Mycobacterium avium complex, primary CNS lymphoma	Cytomegalovirus, M. avium complex, Epstein-Barr virus

Markers

CD4
CCR5
CXCR4
gp120
gp41
p24
reverse transcriptase
integrase

Clinical notes

In Colombia, tuberculosis and histoplasmosis are frequent AIDS-defining illnesses, together with Pneumocystis pneumonia, toxoplasmosis and cryptococcosis.
Starting antiretroviral therapy can unmask or worsen an infection as immunity returns (immune reconstitution inflammatory syndrome).
Prophylaxis against opportunistic infections is chosen according to CD4 thresholds (this page does not give treatments or doses).

In the lab

Screening: fourth-generation immunoassay (HIV-1/2 antibodies plus p24 antigen), confirmed by a differentiation assay and viral load.
Viral load (HIV RNA by PCR): activity of the virus and response to treatment.
CD4 count by flow cytometry: degree of immunodeficiency and risk of opportunistic infections.
In infants of mothers with HIV, diagnosis is by viral nucleic acid tests because maternal IgG crosses the placenta.

Test yourself

Think of the answer, then tap the question to see it.

Which two cell molecules does HIV need to enter a helper T cell?

CD4 and a chemokine co-receptor, CCR5 or CXCR4.

Why does antiretroviral therapy not eliminate HIV?

Integrated, silent provirus in long-lived resting memory CD4 cells (the reservoir) is not touched by the drugs and can restart replication.

Below which CD4 count does the risk of Pneumocystis pneumonia rise sharply?

Below about 200 cells per microlitre.

Where is the largest early loss of CD4 T cells in acute HIV infection?

In the gut mucosal lymphoid tissue, where most CCR5+ memory CD4 cells live.

Why are antibody tests not used to diagnose HIV in young infants of mothers with HIV?

Maternal IgG crosses the placenta and can stay for months; viral nucleic acid tests are used instead.

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Microorganisms

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Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: About HIV (Centers for Disease Control and Prevention (CDC), 2026); 25.3 Viral Infections of the Circulatory and Lymphatic Systems (OpenStax (Microbiology), 2016); 19.4 Immunodeficiency (OpenStax (Microbiology), 2016).

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Representative model, for educational purposes only.