Human immunodeficiency Virus (HIV)

What is Human immunodeficiency Virus (HIV)?

Human immunodeficiency virus (HIV), a genus lentivirus in the retrovirus family, is a deadly virus that poses a major threat to human health. HIV was first detected in France in 1983, and since then, scientists and the medical community around the world have been working hard to study the virus and the diseases it causes. HIV achieves its pathogenic role primarily by attacking and destroying the body's CD4⁺ T cells, which play a central regulatory role in the body's immune system. As HIV continues to infect, the number of CD4⁺ T cells gradually decreases, resulting in a significant decrease in the immune system's defenses, a state known as immunodeficiency. When the immune system is weakened to a certain extent, the body is unable to effectively fight off various external pathogens, so patients are more susceptible to opportunistic infections and develop a range of diseases associated with immunocompromise. This state eventually evolved into AIDS (Acquired Immunodeficiency Syndrome), which represents the advanced stages of HIV infection and is often accompanied by a variety of serious complications. Despite advances in scientific research, HIV remains a major public health challenge for which there is no cure.

Human immunodeficiency Virus structure

The HIV virus is a spherical particle with a diameter of 100~120nm, which is composed of an envelope, an inner shell and a core. The outermost layer of the virus is the envelope, which is a liposome mosaic of outer membrane proteins and transmembrane proteins, the outer membrane protein is gp120, and the transmembrane protein is gp41. Beneath the envelope structure is the inner shell of the virus formed by matrix protein (p17). The core of the virus is composed of capsid protein (p24), which includes two identical viral single-strand positive RNA, RNA-bound nucleocapsid proteins (p7, p9), and reverse transcriptases, integrases, and proteases required for viral replication.

Fig.1 Schematic illustration of a mature HIV-1 virion. (Berthet-Colominas Carmen, et al., 1999)

Causes of morbidity after HIV infection

After HIV enters the human body, its envelope glycoprotein gp120 binds to CD4⁺ T cells (mainly helper T lymphocytes, as well as macrophages, Langerhans cells, etc.) on the surface of CD4 molecules, and promotes HIV to enter target cells through endocytosis of target cells and the melting of gp41. In the nucleus, reverse transcriptase uses viral RNA as a template to transcribe DNA, synthesize double-stranded DNA and integrate into the DNA of the host cell. The other is that the viral DNA sequence is carried by the infected cells and their progeny cells for life, becoming a provirus, entering the incubation period, and once activated by other microorganisms or some chemical agents, it can replicate in large quantities and cause cell death.

In the process of reproduction, HIV continuously kills host cells, reduces the number of CD4⁺ T lymphocytes, and damages mononuclear phagocytic cells, B lymphocytes, CD8⁺ T lymphocytes and NK cells, resulting in immune deficiency and opportunistic infections and tumors in the body.

Fig.2 HIV ENV-mediated membrane fusion and its inhibition. (Melikyan Gregory B, 2014)

Human immunodeficiency Virus transmission ways

Sexual transmission: Sexual transmission is mainly divided into homosexual and heterosexual transmission, and a person can become infected with HIV if they have sex with a person living with HIV without using safe measures. This is also the most common way to get AIDS.

Blood-borne transmission: Sharing a syringe with someone living with HIV can infuse HIV into the bloodstream and cause infection. Even scalpels and blood transfusion equipment used by AIDS patients can become vectors of HIV transmission if they are not properly disinfected.

HIV-related diseases

Common diseases caused by HIV immune dysfunction include:

Tuberculosis (TB): Tuberculosis is the most common infection in clinical practice, but co-infection with Mycobacterium tuberculosis and HIV is the leading cause of death in AIDS patients.

Salmonellosis, candidiasis: AIDS patients have weak resistance and immunity, and are most susceptible to salmonella infection, the main symptoms of salmonellosis are abdominal pain, nausea and vomiting, persistent high fever and chills, etc. Candidiasis is a common HIV-related complication that causes inflammation that can severely damage the health of the mouth, esophagus and vagina.

Renal impairment: HIV can cause damage to the kidneys, leading to tubular necrosis and interstitial nephritis, which can lead to a range of symptoms such as oliguria or anuria, high proteinuria, and high levels of edema. At the same time, it will also increase the heart rate, making the heart enlarge, which can easily cause congestive heart failure.

Long-term diarrhoea: HIV infection can cause long-term diarrhoea, which can lead to water and electrolyte imbalances, which in turn can cause neurological damage. In severe cases, it can lead to mental retardation, unresponsiveness, and some can also lead to mental illness such as depression.

Skin diseases: Symptoms include herpes simplex virus, herpes zoster, seborrheic dermatitis, etc. Among them, the infection caused by herpes simplex virus is related to the number of CD4⁺ T lymphocytes, forming ulcerative lesions in the lips, pubic region and perianal area, and the pain of herpes pustules is obvious.

Tumors: It can lead to the development of tumors, mainly including Kaposi's sarcoma, lymphoma, malignant melanoma, squamous cell carcinoma and so on. Kaposi's sarcoma is commonly found in the nose tip, oral mucosa, trunk, limbs and other sites. The skin lesions of lymphoma are mainly papules or nodules, and malignant melanoma is more common in middle-aged and elderly patients. Squamous cell carcinoma progresses rapidly and can invade connective tissue, cartilage, or metastasize to nearby lymph nodes and internal organs.

Treatment of HIV infection

Although HIV is difficult to completely eradicate, patients cannot be completely cured. However, AIDS can be treated.

Antiviral therapy

Long-term highly effective antiretroviral therapy (HAART), a cocktail therapy, is currently used to treat people with AIDS and HIV. There are more than 30 drugs (including combination drugs) in 6 categories on the market, namely nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors (INSTIs), membrane fusion inhibitors (FIs) and CCR5 inhibitors. The main antiretroviral drugs available are Tenofovir-disoproxil (TDF), Abacavir (ABC), Lamivudine (3-TC), Emtricitabine (FTC), Zidovudine (AZT).

Immunomodulatory therapy

HIV infection is a chronic, progressive immunodeficiency disease that uses a variety of immunotherapies to enhance the immune function of infected individuals to slow the progression of the disease. The drugs mainly used for immune regulation are Interferon α, IL-2, amma globulin, and traditional Chinese medicine (such as lentinan mushroom, salvia, astragalus and glycyrrhizic acid, etc., all have the effect of regulating immune function).

Malaria therapy

Malaria therapy researchers have tried malaria therapy to treat AIDS, through a strong malaria infection, the lymphocytes and other swimming cells in the patient's body are redistributed, so that it is possible to expel the HIV hidden in it, so that this long-lived dormant cell becomes a short-lived awakened cell, thus releasing HIV hidden in the cell genome.

References

• Melikyan, Gregory B. HIV entry: a game of hide-and-fuse?. Current opinion in virology 4 (2014): 1-7.
• Berthet-Colominas, Carmen, et al., Head-to-tail dimers and interdomain flexibility revealed by the crystal structure of HIV-1 capsid protein (p24) complexed with a monoclonal antibody Fab. The EMBO Journal (1999).

※ Please kindly note that our services are for research use only.