How does a tiny virus with a diameter of less than 120 nanometers carry out its "T cell attack plan" in the human body?

On June 5, 1981, the U.S. Centers for Disease Control and Prevention announced five cases of Pneumocystis carinii pneumonia, whose symptoms were very similar: persistent high fever, significant weight loss, and almost complete collapse of the immune system... A few months later, a new infectious disease began to enter people's field of vision, which was acquired immunodeficiency syndrome - AIDS (Acquired Immunodeficiency Syndrome) . These special cases became the world's first official records of AIDS.

More than 40 years have passed, and AIDS is still a health challenge facing mankind. According to the latest report released by the United Nations AIDS Program, there are currently about 39 million people infected with HIV (Human Immunodeficiency Virus) in the world, and in 2022 alone, there will be about 1.3 million new HIV infections worldwide. The reason why AIDS is so terrifying is that after HIV invades the human body, it directly invades the human immune system. How does this tiny virus attack the human immune system? Is it possible for us to completely cure AIDS in the future ?

Schematic diagram of HIV virus particles

Image source:

https://www.cdc.gov/nchhstp/newsroom/multimedia-resources/hiv-multimedia-resources.html

01 HIV’s invasion mechanism

HIV, scientifically known as human immunodeficiency virus, is about 100 to 120 nanometers in diameter and is round or oval in shape. Its genome is two identical single-stranded positive-strand RNAs. Compared with the double-stranded structure of DNA, the single-stranded structure of RNA is more susceptible to genetic mutations. The HIV invasion mechanism involves a series of complex biological processes that enable the virus to enter host cells and begin to replicate:

(1) Invasion of host cells

The main target of HIV attack is the CD4+T lymphocytes, which are the most important part of the human immune system. First, it binds to the host cell surface receptor: There is a protein called gp120 on the outer membrane of HIV, which can bind to the CD4 receptor on the surface of the host cell. This is the first step for the virus to invade.

Binding to co-receptors: In addition to binding to the CD4 receptor, HIV also needs to bind to co-receptors on the surface of host cells in order to more firmly invade the cells. The most common co-receptors are CXCR4 or CCR5. Different HIV strains may use different co-receptors.

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(2) Launch a frenzied attack

Next, HIV continues to charge forward, and once it binds to the CD4 receptor and the co-receptor, it undergoes a fusion process in which the outer membrane of the virus fuses with the membrane of the host cell. This allows the virus to inject its genetic material (RNA) into the interior of the host cell like a "master of disguise."

HIV carries a reverse transcriptase. When the virus's genetic material enters the host cell, it is quickly transcribed into DNA with the help of reverse transcriptase , just like a new "copy" of the virus is produced. Then, the viral DNA is integrated into the host cell's genome under the action of another enzyme (integrase). This viral DNA integrated into the host DNA is called a "provirus."

In this way, HIV begins to multiply and take root in the body. These "proviruses" are activated and transcribe themselves to form viral RNA. At the same time, under the action of proteases, the structural and non-structural proteins of the virus are synthesized. These new viral components will eventually assemble into new HIV virus particles, ready to infect other host cells, especially CD4+T lymphocytes, leading to the spread of infection and gradual damage to the immune system.

HIV virus replication process Source: STD and AIDS Prevention and Control Center

The HIV attack process may seem like a "flood and beast", but for the clinical symptoms of the infected person, it can also be regarded as a "relatively long" process.

In the early stage of infection (acute infection) , many people may not have obvious symptoms, but at this time HIV has already replicated rapidly in the body, and a small number of infected people may also experience fever, chills, rash, fatigue and other cold-like symptoms. But who doesn't have a headache or fever occasionally? These symptoms are often ignored, which undoubtedly gives HIV a chance to wreak havoc.

After the acute infection period, there is an asymptomatic period , which may last for several years or even more than ten years. During this period, the virus continues to replicate, but the symptoms may not be obvious. At this time, the patient is called "asymptomatic HIV-infected person". Although it seems no different from a normal person, the virus is still multiplying crazily at this moment, destroying the human immune function. If not treated, HIV infection may eventually develop into AIDS.

AIDS is a state in which the immune system is severely impaired. Since the body's cellular immune function has become difficult to maintain, the infected person completely loses the ability to resist external viruses and bacteria and enters the final stage of HIV infection, the "AIDS stage". Patients are extremely prone to serious opportunistic and malignant tumors .

02 There have been several cases of people cured of AIDS around the world. Can the method of conquering AIDS be replicated?

HIV's "T cell attack plan" is a complex and cunning process. This complex invasion mechanism allows HIV to continuously infect and destroy the host's immune system, leading to immune system disorders and the development of AIDS. However, researchers have been working hard to study this process and seek new ways to prevent infection and treat AIDS.

With the scientific and technological progress in the field of AIDS prevention and treatment, biomedical intervention measures with AIDS antiviral drugs as the core have gradually developed and improved, which can effectively inhibit the replication of HIV, slow the progression of the disease, improve the quality of life of patients, and reduce the spread of the virus. Due to the improved effectiveness of antiviral treatment, the prognosis of AIDS has been significantly improved. Many patients are able to maintain a healthy state for a long time and are called "Long-Term Non-Progressors" (LTNP), and they will not quickly develop AIDS.

"Golden 72 Hours of Self-Help", also known as HIV post-exposure prophylaxis (PEP), is a biomedical intervention measure that uses antiviral drugs to block the spread of HIV after exposure . It is an important part of the comprehensive AIDS intervention strategy. Post-exposure prophylaxis provides an opportunity for emergency blocking for people at high risk of HIV exposure, helping to reduce HIV infection and transmission. It has been widely promoted and applied around the world.

On July 20 this year, according to the ABC News, French and Swiss researchers confirmed the latest man in long-term remission of HIV, known as the "Geneva patient," who is the sixth AIDS patient in the world to achieve long-term remission . What is even more optimistic is that he did not receive the same allogeneic bone marrow transplant with the CCR5△32 gene mutation that is resistant to HIV as the previous five patients. This makes people wonder whether it means that there will be more treatments to fight the "curse" of AIDS?

Image source: IAS 2023 (International AIDS Society)

This HIV patient, known as the "Geneva patient," achieved long-term remission without undergoing traditional gene transplantation, suggesting that the path to treating AIDS may be more diverse and individualized. Over the years, the use of antiviral drugs has significantly improved the survival of AIDS patients, but cure remains challenging. The virus is highly variable, and universal therapy is not easy to achieve. Therefore, scientists are exploring new strategies such as gene therapy and immunotherapy in order to achieve long-term remission or cure for more patients.

The case of the "Geneva patient" highlights the promise of diversified treatments that do not rely solely on traditional methods . This personalized treatment may better meet the needs of different patients. Although the road is long, there is hope in the field of HIV treatment, and scientists will persist in their efforts to eventually overcome this global challenge. New cure cases and research results bring hope to the future, so that patients can live a healthy and happy life.

The transmission of HIV is not limited to sexual intercourse, but also includes mother-to-child transmission, blood transmission, etc. In addition, early diagnosis is crucial for early initiation of antiviral treatment, reducing the risk of HIV transmission, and improving the quality of life of patients.

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Today is the 36th World AIDS Day . Through popularizing health education and taking appropriate preventive measures such as using condoms, avoiding sharing syringes, accepting HIV testing, and providing mother-to-child prevention measures, we can reduce discrimination, panic and virus transmission, thereby better controlling and preventing AIDS.

References:

[1] Centers for Disease Control (CDC). Persistent, generalized lymphadenopathy among homosexual males. Morbidity and Mortality Weekly Report.. 1982 May 21;31(19):249-51.

[2] Centers for Disease Control (CDC). Update on acquired immune deficiency syndrome (AIDS) – United States. Morbidity and Mortality Weekly Report. 1982 Sep 31 (37): 507–08, 513–14.

[3] http://www.unaids.org.cn/

Author: Tang Wei, deputy chief physician of the Department of Infection and Immunity, Changsha First Hospital

Reviewer: Li Nannan, second-level researcher of Hunan Association for Science and Technology, director of Hunan Science Writers Association, expert on popular science in China

Chen Yuefei, Researcher, Member of Hunan Science Writers Association, Expert on Science Popularization in China

Produced by: Science Popularization China

Produced by: China Science and Technology Press Co., Ltd., China Science and Technology Publishing House (Beijing) Digital Media Co., Ltd.