Primates and AIDS

December 1, 2022 is the 35th "World AIDS Day". This year, the theme of my country's publicity campaign is "Fighting AIDS Together and Sharing Health", emphasizing that everyone should participate and work together to cope with the risks and challenges brought by the AIDS epidemic, and advocating for the whole society to build, govern and share together. Compared with the new coronavirus, HIV has been a resident virus of humans for nearly a hundred years, but there is still no drug or method to completely cure it. They are both viruses, why can the former develop a corresponding vaccine while HIV cannot? Who exactly is HIV? Let me tell you.

1. How much do you know about AIDS?

You must be familiar with the name of AIDS. It is one of the most serious epidemics known in the world so far. It is also called acquired immunodeficiency syndrome (AIDS). This disease is caused by infection with the human immunodeficiency virus (HIV). It will seriously damage our human immune system and cause a variety of clinical symptoms. HIV is a spherical RNA virus with a diameter of about 100~120nm. It consists of two parts: the envelope and the core. The envelope is embedded with two proteins involved in identifying host cells; the envelope contains matrix proteins and semi-conical capsids, as well as various enzymes necessary for viral proliferation; the core contains two RNA chains, which are the genetic material for viral replication. The structure is so simple, but it is a nightmare for humans!

HIV structure diagram

HIV model

01

How does HIV cause disease?

The main targets of HIV attack are human lymphocytes (CD 4+ T cells) and macrophages, and CD 4+ T cells are the main cells that play an anti-HIV immune role and are also the target cells attacked by HIV. When the cunning virus enters the cell to attack, it will quickly replicate to enhance its strength. The immune cells will not show weakness and will fight back. At this time, the replication and clearance of the virus will reach a relatively balanced stable state. However, this balance will eventually be broken. As the number of CD 4+ T cells continues to decline in the long-term battle, when the number of CD 4+ T cells is lower than a certain level, the immune function of the infected person will be severely damaged, eventually leading to immunodeficiency.

HIV infects CD4+ T cells by binding to the CD4 receptor and CCR5 coreceptor on the cell surface

02

What are the clinical manifestations?

About half of all people who are HIV-positive will develop AIDS within 10 years of infection. The average incubation period of AIDS is 6-8 years, but it can be as short as a few months or as long as decades. It is divided into the acute phase, the latent phase and the AIDS phase. In the acute phase, widespread viremia occurs, and the main clinical manifestations are fever, sore throat, night sweats, nausea, vomiting, diarrhea, rash, joint pain, swollen lymph nodes and neurological symptoms. The body will not show any symptoms during the latent phase, but the virus can be detected in most lymphoid organs. The AIDS phase is the final stage after HIV infection, and the main clinical manifestations of this phase are AIDS-related symptoms, various opportunistic infections and tumors.

Clinical manifestations

HIV-infected T cells (color scanning electron micrograph)

Common clinical manifestations of AIDS

2. Unveiling the mystery

The understanding of AIDS has gone through many twists and turns. The first time HIV infected humans was discovered in Africa, when a male patient from the Bantu tribe in Congo, Africa, died of an unexplained disease. However, due to the limited knowledge at the time, the patient was misdiagnosed as sickle cell anemia. The blood sample drawn from him in 1959 has been preserved to this day. Many years later, it was found to contain HIV virus after retesting. Therefore, it is speculated that HIV had been transmitted among humans before 1959, and the man became the first confirmed HIV infected person. AIDS was discovered in Africa and later brought to the United States by immigrants. The first case was reported in the United States in 1981, when five healthy young people in Los Angeles suffered from Pneumocystis carinii pneumonia. This infection is relatively rare and generally only occurs in patients with severely weakened immune function, such as malnourished infants, transplant patients, and chemotherapy patients. The condition of these five young people deteriorated rapidly, and two patients had died when it was reported. A month later, doctors confirmed more similar cases. In New York and California, 26 young and healthy men were diagnosed with Pneumocystis carinii pneumonia or Kaposi's sarcoma. Kaposi's sarcoma is a rare malignant tumor that also only occurs in people with weakened immune function. These cases attracted the attention of the US Centers for Disease Control and Prevention, and everyone realized that a new disease might have emerged, and officially named it AIDS in 1982. However, at that time, people had no idea about it, and didn't even know whether it was an infectious disease, poisoning, or radioactive pollution. People were panicked, and traffic police in New York even wore masks for prevention. Half a year later, the Centers for Disease Control and Prevention had counted 159 such cases, and more and more cases told people that this might be a dangerous new infectious disease. With the emergence of AIDS cases, human research on the virus has also deepened step by step, and great research progress has been made. In 1983, the Pasteur Institute in Paris, France, and in 1984, researchers from the National Institutes of Health and the University of California, San Francisco, successively isolated AIDS-related viruses from AIDS patients. However, although new viruses were found in the immune cells of patients, this was not a complete success. What if this virus is not related to the new disease? Scientists quickly developed a simple and sensitive virus detection technology, and then collected blood samples from patients around the world and tested them one by one, and found that the virus was indeed widely present in all patients, but not in healthy people. In 1986, the International Microbiological Association and the Virus Taxonomy Association uniformly named it human immunodeficiency virus (HIV), or AIDS virus. So far, HIV has become the most clearly studied virus in the world.

Initial reports in 1981 (CDC)

Gaetan Dugas, "Patient Zero"

An AIDS patient who has survived for 30 years after being infected. The dark marks on his face and arms are Kaposi's sarcoma (New York Times)

3. Find the real culprit

There are currently four known HIV strains, namely M, N, O, and P. The most widely spread M and N have been confirmed to come from chimpanzees in Cameroon, and O and P come from gorillas in southwestern Cameroon.

So, you may ask how HIV spread from chimpanzees to humans? In fact, until now, scientists have not been able to figure out how HIV spread from chimpanzees to humans. The more popular theory is that the hunting and slaughter of apes caused the virus to be transmitted to humans, mutated in the human body, and eventually led to human-to-human transmission. HIV is more deadly to humans, while chimpanzees are generally not seriously infected with HIV. This may be the result of SIV co-evolving and coexisting in monkeys for a long time.

4. How is HIV transmitted? Are we really powerless?

HIV mainly exists in the blood, semen, vaginal secretions, breast milk and other body fluids of the infectious source. It can be transmitted through direct contact with mucous membrane tissues such as the mouth, genitals, and anus. The main routes include: unsafe same-sex, heterosexual, and bisexual contact; sharing needles for intravenous drug use; mother-to-child transmission, including intrauterine infection, delivery, and breastfeeding; blood transfusions and the use of blood products.

The main carriers of HIV

HIV infection and transmission

Although HIV is highly contagious, it has a weak ability to survive in the external environment. It is sensitive to heat but highly tolerant to low temperatures. Although ultraviolet rays or gamma rays cannot inactivate HIV, pasteurization and the common concentrations of most chemical disinfectants can inactivate HIV. Normal life contact will not transmit AIDS, because it can only survive in living cells in blood and body fluids, and cannot survive in air, water, and food. Without these blood and body fluids, these viruses will die quickly. Air itself cannot kill HIV, but exposure to air will dry out body fluids containing HIV, and the virus will be quickly destroyed. And like the hepatitis B virus, it will be destroyed by the protease in the digestive tract after entering the digestive tract. The US CDC report stated that drying for a few hours can reduce the activity of the virus by 90-99%, and it can only be transmitted through direct contact between people with the blood or body fluids of infected people.

According to existing data, there are more than 40 million HIV-infected people in the world, and the total number of AIDS cases has exceeded 5 million. The largest number of AIDS patients is in the Americas, followed by Asia and Europe. Since the first case of AIDS was reported in China in 1985, the prevalence of AIDS has been rising rapidly. At present, through strengthening detection and innovative treatment strategies, AIDS-infected people can be discovered and treated to the greatest extent, and prevention and control work has made significant progress. As of the end of October 2019, 958,000 surviving infected people were reported nationwide, and the overall epidemic continued to be at a low prevalence level. The high mortality and disability rates of AIDS cause patients to suffer a lot of pain and pressure. Because of its rapid mutation, vaccine development is very difficult and is still a long way off. But there are also some lucky patients who have been cured miraculously. For example, in 1995, an American translator named Timothy Ray Brown, who once lived in Berlin, Germany, was found to be carrying HIV and was later diagnosed with acute leukemia. His attending physician used the principle that people with CCR5 gene defects can prevent HIV from attacking the immune system and transplanted the bone marrow of a matching person with CCR5 gene defects. HIV miraculously disappeared from his body and he became the only AIDS patient cured in the world. People also called him the "Berlin patient" (ps: later there was a cured "London patient"). Although there are cured patients around the world, these treatments are very expensive and difficult. To date, HIV-infected patients are still considered incurable.

The Berlin Patient

But the good news is that scientists have developed antiretroviral drugs in 1987. The "cocktail therapy" developed by Americans can inhibit the replication of the virus to the maximum extent, and partially or even completely restore the damaged immune system. It is a therapy that uses a combination of multiple antiviral drugs to fight the virus. Today, AIDS has changed from a death sentence to a controllable chronic infectious disease, saving the lives of tens of millions of people around the world.

5. Reflections on AIDS

AIDS prevention deserves everyone's attention and participation. AIDS originated from the initial close contact between humans and wild animals, which reminds us to always maintain awe in the process of contacting nature and obtaining natural resources. At the same time, we need to increase investment in basic research to be fully prepared for the prevention and control of possible cross-species human-to-human transmission of viruses.