In the class, we discussed HIV-1 capsid, a metastable megadalton assembly that protects the viral genome and is responsible for the spread of viral infection.

QUESTION

Question 1. In the class, we discussed HIV-1 capsid, a metastable megadalton assembly that protects the viral genome and is responsible for the spread of viral infection. To prevent retroviral infections, however, their mammalian hosts express a variety of proteins, termed host-restriction factors. One of the most well-known restriction factor in this evolutionary tug of war against retroviruses is a protein called TRIM5α. Use the accompanying manuscript as a guide, Ganser- Pornillos and Pornillos, Nature Reviews Microbiology 2019 (Figs. 3 and 4), to summarize the mechanism with which this protein attempts to nullify retroviral infection. Also comment on why this protein is not that successful in preventing the spread of HIV-1. (page 553 of this manuscript).

(400 words; 20 points)

Question 2. We talked about rabies in the class – one of the most fatal diseases known to mankind. Summarize the life cycle of rabies virus using the accompanying manuscript as a guide, Schnell et al., Nature Reviews Microbiology 2010 (Fig. 3). Note: I am looking for a general summary and not precise details of each step. (300 words; 15 points)

Question 3. A process known as “antigenic drift” is responsible for blunting the effect of vaccine against influenza. In addition, influenza A, only known strain to cause pandemics, employs a process called “antigenic shift”. Briefly explain these two processes. In addition, using the accompanying manuscript as a guide, Kim et al., Viral Immunology, 2018 (page 175-176, Fig. 1), summarize the strategies that are used by influenza virus to evade host-immune response.

(400 words; 15 points)

ANSWER

Question 1 Summary

The manuscript by Ganser-Pornillos and Pornillos in Nature Reviews Microbiology 2019 focuses on the protein TRIM5α and its role as a host-restriction factor in preventing retroviral infections, specifically targeting HIV-1. TRIM5α is known for its attempts to nullify retroviral infection by recognizing the capsid protein of the virus.

The mechanism employed by TRIM5α involves the recognition of the viral capsid through its C-terminal B30.2/SPRY domain. This recognition triggers the recruitment of TRIM5α to the incoming virus and promotes the formation of higher-order oligomers, leading to the disruption of the viral capsid. This disruption inhibits the viral replication process and prevents the spread of the infection.

However, despite its efforts, TRIM5α is not entirely successful in preventing the spread of HIV-1. This is primarily due to the ability of HIV-1 to counteract TRIM5α-mediated restriction through various strategies. The viral capsid of HIV-1 has evolved to evade recognition by TRIM5α, thereby allowing the virus to replicate and propagate within the host cells. Additionally, HIV-1 encodes accessory proteins, such as Vif, which can counteract TRIM5α-mediated restriction by targeting TRIM5α for degradation.

The manuscript sheds light on the ongoing evolutionary battle between retroviruses and host-restriction factors like TRIM5α. While TRIM5α acts as a potent defense mechanism, retroviruses like HIV-1 have developed countermeasures to evade its restrictive effects, highlighting the complexity and adaptability of viral-host interactions in the context of retroviral infections.

Question 2 Summary

The manuscript by Schnell et al. in Nature Reviews Microbiology 2010 provides insights into the life cycle of the rabies virus, one of the most fatal diseases known to mankind. The general summary of the rabies virus life cycle can be outlined as follows:

Entry and Attachment: The rabies virus enters the host’s body through the introduction of infected saliva, typically through a bite from an infected animal. The virus then attaches to specific receptors on the surface of nerve cells.

Neural Invasion: The virus undergoes retrograde transport within the nerves, traveling towards the central nervous system (CNS). It exploits the neuronal transport machinery to reach the CNS rapidly.

Replication in CNS: Once inside the CNS, the virus begins to replicate within the nerve cells, leading to the spread of infection throughout the nervous system.

Axonal Transport and Peripheral Infection: The virus utilizes axonal transport to move from the CNS to various peripheral tissues, primarily targeting salivary glands. Replication occurs in these peripheral tissues, leading to viral shedding into saliva.

Transmission: The virus is transmitted to a new host primarily through the bite of an infected animal, allowing the cycle to continue.

The manuscript provides a more detailed understanding of the specific molecular interactions and cellular processes involved at each step of the rabies virus life cycle.

Question 3 Summary

Antigenic drift and antigenic shift are two important processes associated with the influenza virus and its ability to evade the host immune response.

Antigenic drift refers to the gradual accumulation of mutations in the genes that encode the surface proteins of the influenza virus, namely hemagglutinin (HA) and neuraminidase (NA). These mutations result in small changes in the antigenic properties of the virus over time. As a result, the antibodies produced by the host immune system, either through natural infection or vaccination, become less effective in recognizing and neutralizing the drifted strains of the virus. This is a continuous process that occurs within a specific subtype of influenza A or B virus.

On the other hand, antigenic shift is a more dramatic process that involves the reassortment of genetic material between different strains of influenza viruses, leading to the emergence of a novel subtype. This occurs when two different influenza viruses infect the same host cell and exchange genetic segments. Antigenic shift can result in the generation of a completely new subtype of the virus, to which the population has little to no pre-existing immunity. This can lead to the outbreak of pandemics, as seen in the case of influenza A viruses such as H1N1 and H2N2.

The manuscript by Kim et al. in Viral Immunology 2018 highlights several strategies employed by the influenza virus to evade the host immune response. These include antigenic variation through antigenic drift and shift, glycosylation masking to hide vulnerable epitopes, modulation of host immune responses, and interference with host antiviral pathways. These evasion strategies allow the influenza virus to persist and cause recurrent infections in human populations, posing challenges for effective vaccine development and control measures.