What is an Adenovirus?

Adenovirus is a kind of particles with a diameter of 70 to 90 nm without an envelope. It consists of 252 shell particles arranged in a physahedron. The diameter of each crust is 7-9 nm. The capsid is a linear double-stranded DNA molecule that contains approximately 4.7 kb with inverted repeats of approximately 100 bp at each end. Since the 5 end of each DNA strand is covalently bonded to a protein molecule with a relative molecular mass of 55 × 10 ³ Da, a circular structure of double-stranded DNA can occur.

Adenovirus

There are 52 known human adenoviruses, named adl ad52, and the most detailed study is ad2. gland

Adenovirus

Classification and since the discovery and successful isolation of adenoviruses in the 1950s, more than 100 serotypes have been discovered, of which there are 52 human adenoviruses, divided into six sub-groups A, B, C, D, E and F Subgroup. Gene type 2 and type 5 adenoviruses commonly used in gene therapy belong to subgroup C in serological classification, and have 95% homology in DNA sequence. The proliferation ability of the two is very strong, the titer can usually reach 109 pfu (plaque forming unit) / ml, and its genome copy number in a single cell can reach 104 (about 10% of the total DNA of the cell). The virus particles are relatively stable and can reach 1010 ~ 1011 pfu / ml by CsCl gradient centrifugation, which meets the requirements of animal experiments.

Adenoviruses affect the respiratory, gastrointestinal,

The adenovirus life cycle can be divided into two distinct phases that cannot be separated. The first stage involves adenoviral particle attachment and entry into host cells, release of the genome into the host cell nucleus, and selective transcription and translation of early genes. At this stage, the cells are ready for viral genome replication and adenovirus late gene expression and finally release mature infectious particles, the second stage. The first phase will be completed in 6-8 hours, and the second phase is faster, which only takes 4-6 hours.

Adhesion and entry into cells

The process of adenovirus infecting cells begins with the adenovirus ciliary ganglion region adhering to specific receptors on the cell surface. Because human adenovirus mainly shares a receptor with Coxsackie B virus, this receptor is called coxsackie / adenovirus receptor (CAR). Next, the tripeptide RGD on the surface of the penton of the viral ciliary base binds to v3 and v5 integrin on the cell surface, and internalizes the adenovirus into the cell and enters the lysosome through endocytosis. In the acidic environment of the lysosome, the conformation of the adenovirus capsid will change, and it will be released from the lysosome to escape the digestion of the lysosome. Finally, the adenovirus particles are translocated to the nucleus, and the viral DNA is released into the nucleus through the nuclear pore. Compared with liposome transfection, the adenovirus genome enters the nucleus is a very efficient process, which can generally reach 40%. Although the former enters the cytoplasm with an efficiency comparable to the latter, the DNA enters the nucleus with only 1 / 1000.

Transcription and replication

Once the viral genome enters the nucleus, a series of complex and orderly progressive amplification and shearing processes are performed. Generally, the viral DNA begins to copy as a dividing line, and the adenovirus genes are roughly divided into early (E1 ~ 4) and late transcription units (L1 ~ 5) according to the sequence of transcription time. Various adenovirus genes can be further divided into smaller transcription units. For example, the E1 region can be further divided into E1A and E1B. Each transcription unit has at least one unique promoter. After the adenovirus genome enters the nucleus, the cell

Adenovirus inactivated formaldehyde vaccines have been used for prevention in some populations, and may be replaced by live attenuated vaccines using human diploid cell culture in the future. However, because adenoviruses have carcinogenic effects on animals, people have doubts about the role and safety of whole virus vaccines. In addition, strengthening the disinfection of water in swimming pools and baths can minimize the risk of water-borne conjunctivitis outbreaks. Strictly aseptic operations should be performed during eye examinations. The equipment used should be fully sterilized and epidemic conjunctivitis can be controlled happened. There are still no effective drugs for the treatment of adenovirus infections.

Main functions of adenovirus gene products

E1 region gene expression product

It can be further divided into E1A and E1B. E1A is mainly composed of two components, namely 289R (or 13S) and 243R (or 12S). The main function of these E1A proteins is to regulate cell metabolism and make cells more susceptible to virus replication. E1B19K is homologous to the expression product of the cell Bcl-2 gene, and can prevent apoptosis or necrosis by inactivating and eliminating members of the Bax family. E1B55K gene product can be down-regulated

Wide range of hosts Low human pathogenicity

Adenovirus vector systems are widely used for the expression of human and non-human proteins. Adenoviruses can infect a range of mammalian cells, so they can be used to express recombinant proteins in most mammalian cells and tissues. It is important to point out that adenoviruses are epithelial, and most human tumors are derived from epithelial cells. In addition, the replication genes and pathogenic genes of the adenovirus are quite clear and have been circulating in the population (70-80% of adults have neutralizing antibodies for adenovirus). Human infection with wild-type adenovirus produces only mild self-limiting symptoms, and ribavirin treatment is effective.

Infect and express genes in proliferating and non-proliferating cells

Adenovirus infections are mainly epidemic in winter and spring and are prone to outbreaks in kindergartens, schools and barracks recruits. In general, adenovirus is mainly transmitted through respiratory tract droplets, eye secretions, or through respiratory tract or contact; intestinal infections are mainly transmitted through the digestive tract. Its preventive measures are similar to the prevention of other infectious diseases of the respiratory tract and digestive tract. It is mainly to wash hands and disinfect frequently to avoid contact with patients and their respiratory droplets. Drink plenty of water, eat more vegetables and fruits, pay attention to exercise; ventilate indoors to keep the indoor environment clean; try to avoid crowded public places during winter and spring seasons, and wear masks when going out to avoid contact with patients to prevent infection.

As soon as the symptoms of acute fever, sore throat and conjunctivitis occur, it is necessary to go to the hospital as early as possible for isolation and early treatment. Report collective outbreaks of more than five people to the local epidemic prevention department in a timely manner, and take effective prevention and control measures in a timely manner to avoid the spread of the disease. In the adenovirus epidemic season, children with upper respiratory tract infections in childcare institutions should go home and rest to avoid spreading the epidemic. After getting sick, try to see a doctor in a nearby hospital to avoid infusion in the observation room of a large hospital where patients are more concentrated, to prevent cross infection. The symptoms of severe cough and dyspnea are mostly serious cases, and they should be hospitalized in time to avoid delay.