Zika virus may affect the male reproductive system

  A few days ago, the World Health Organization announced at its headquarters in Geneva, Switzerland that Zika virus and the neurological diseases caused by it no longer constitute a "public health emergency of international concern." In the future, WHO will switch to relying on a long-term mechanism to respond to this significant and continuing public health challenge.

  Although the WHO has removed the Zika virus from the list of public health emergencies, the impact of this virus and the many scientific puzzles behind it are still driving the continuous work of scientists around the world.

  In the early morning of November 22, Beijing time, the international academic journal "Cell" published online a new discovery made by the research team of Professor Li Xiangdong of China Agricultural University and the team of Gao Fu, a researcher at the Institute of Microbiology of the Chinese Academy of Sciences and an academician of the Chinese Academy of Sciences. This joint team from China found that Zika virus can cause testicular damage and eventually lead to male sterility in a mouse model. This discovery reveals the possibility of Zika virus affecting human health from a new perspective.

  "low-key" Zika

  Zika virus is an arbovirus, the main host is wild primates and mosquitoes living on trees. Zika virus, like other members of the flavivirus genus, such as dengue fever, Japanese encephalitis, and West Nile virus, is mainly transmitted through mosquito vectors.

  This virus is not new. It was discovered in rhesus monkeys in the Zika jungle of Uganda as early as 1947, but it has not formed a “climate”. It was not until 2015 when the Zika virus broke out in South America that it became a public health issue of international concern. As of November 10, 72 countries and regions around the world have reported the spread of Zika virus within their borders.

  The incubation period of Zika virus is about 3 to 12 days, and it recovers in 2 to 7 days after the onset. Most people have no obvious symptoms. Only about 20% of infected people will show mild symptoms, such as acute low-grade fever, maculopapular rash, joint pain, conjunctivitis, headache, etc.

  It seems that the Zika virus seems very "low-key" compared with the "bloody" Ebola virus. However, since last year, about 2,000 newborns in Brazil have been diagnosed with microcephaly, and this phenomenon is accused of being related to Zika virus infection in pregnant women, which has quickly become a hot spot for scientists around the world.

  “In the past, researchers’ concerns about Zika virus were mainly focused on fetal abnormalities such as miscarriage, neonatal microcephaly, and Guillain-Barré syndrome,” Gao Fu said, “but in May 2016, a clinical journal reported This means that Zika virus can be transmitted through sex, and Zika virus RNA can exist in human semen for a long time, suggesting a new way of transmission of Zika virus and a potential threat to human health."

  So, Gao Fu, who specializes in emerging infectious diseases, quickly teamed up with Li Xiangdong, who is dedicated to reproductive health research, to form a joint research team to try to unearth the secrets of Zika virus.

  "Killer" surfaced

  The truth is surprising. The joint research team found that mice infected with Zika virus can still find the virus in the testes of male mice that can survive for several weeks even after the virus is no longer detected in the blood. After Zika virus infects the male reproductive system of mice, it will trigger a series of pathological processes, causing testicular damage and ultimately leading to male infertility.

  "This means that the Zika virus has broken through the blood-testis barrier." Li Xiangdong said, "This is an immune barrier for humans and many animals. It can block the antigenicity of sperm, prevent the body from producing anti-sperm antibodies, and avoid autoimmunity. Reaction; It can also prevent harmful substances from affecting the sperm production of mammals and humans, or damage the sperm that has formed, thereby protecting the microenvironment of sperm production."

  Once the

   virus breaks through the blood-testis barrier, it causes testicular interstitial hyperemia, acute orchitis, and epididymitis on the 8th day after infection. The testis and epididymis tissues are significantly atrophy, and the testosterone level is significantly reduced. On the 16th day, a large number of sperm cells died and the seminiferous tubes of the testes were gradually lost. On the 30th day of infection, the testes further shrank, and the seminiferous tubes further lost their normal structure; on the 60th day, the testes completely atrophy and lost their tissue structure.

  Researchers further discovered that in the reproductive system of male mice, Zika virus specifically infects the testes and epididymis, but not the prostate and seminal vesicle glands. Zika virus first specifically infects stem cell-like cells in the testis-peritubular muscle-like cells and spermatogonia. Sertoli cells and mesenchymal cells in the testis, as well as epithelial cells in the epididymis, will produce a large number of pro-inflammatory cytokines and chemokines after Zika virus infection, while peritubular myocytes and spermatogonia have no cytokines. produce.

  "The harm of Zika has not peaked yet"

  The research team further traced the virus's "footprint" and found that Zika virus entered the cell through a co-receptor expressed by peritubular myoid cells and spermatogonia-AXL, indicating that these two cells may be Zika The main target cell of virus infection.

  "Because the peritubular muscle-like cells and spermatogonia cannot produce large amounts of pro-inflammatory cytokines and chemokines, Zika virus is not easily cleared, resulting in damage to the structure and function of the testis; in addition, the stem cells of these two types of cells Such characteristics will directly affect the regeneration of damaged testicles caused by virus infection, and eventually lead to male sterility." Li Xiangdong said.

  This discovery found the scientific basis for the transmission of Zika virus through semen, and also suggested the further harm caused by the virus through sexual transmission. As the deputy director of the Chinese Center for Disease Control and Prevention, Gao Fu is very vigilant about this characteristic of the virus: "China has just opened the two-child policy, then the Zika virus may affect the health of our next generation. It is recommended that the country attaches great importance to this. Prevention and control of this kind of virus."

  Researchers hope that the international medical community and public health policy-making agencies will attach great importance to the risk of Zika virus to reproductive health, especially the new testing methods of existing sperm banks and long-term follow-up of men who have been clinically infected with Zika virus.

  "Existing research has proved that Zika virus is a typical virus that can break through the four major immune barriers of humans." Gao Fu said, "The harm of Zika virus has not yet peaked. As more and more With the emergence of clinical and basic research results, the damage of Zika virus to humans will exceed people's initial imagination. The war between humans and Zika virus may have just begun."