Early during the infection process, rotavirus causes the shutoff of cell protein synthesis, with the nonstructural viral protein NSP3 playing a vital role in the phenomenon. In this work, we have found that the translation initiation factor 2␣ (eIF2␣) in infected cells becomes phosphorylated early after virus infection and remains in this state throughout the virus replication cycle, leading to a further inhibition of cell protein synthesis. Under these restrictive conditions, however, the viral proteins and some cellular proteins are efficiently translated. The phosphorylation of eIF2␣ was shown to depend on the synthesis of three viral proteins, VP2, NSP2, and NSP5, since in cells in which the expression of any of these three proteins was knocked down by RNA interference, the translation factor was not phosphorylated. The modification of this factor is, however, not needed for the replication of the virus, since mutant cells that produce a nonphosphorylatable eIF2␣ sustained virus replication as efficiently as wild-type cells. In uninfected cells, the phosphorylation of eIF2␣ induces the formation of stress granules, aggregates of stalled translation complexes that prevent the translation of mRNAs. In rotavirus-infected cells, even though eIF2␣ is phosphorylated these granules are not formed, suggesting that the virus prevents the assembly of these structures to allow the translation of its mRNAs. Under these conditions, some of the cellular proteins that form part of these structures were found to change their intracellular localization, with some of them having dramatic changes, like the poly(A) binding protein, which relocates from the cytoplasm to the nucleus in infected cells, a relocation that depends on the viral protein NSP3.While every step of the translation process is amenable to regulation, under most circumstances mRNA translation primarily is regulated at the level of initiation (8). The translation of eukaryotic mRNAs involves the recognition and recruitment of mRNAs by the translation initiation machinery and the assembly of the 80S ribosome on the mRNA; this process is mediated by the eukaryotic initiation factors (eIFs). Translation initiation is a complex process that begins with the recognition of the cap nucleotide structure (m7GpppN) at the 5Ј end of mRNAs by the cap binding protein eIF4E, which is part of the cap binding complex eIF4F. This complex is composed of eIF4E, eIF4A (which is an ATP-dependent RNA helicase), and the scaffolding protein eIF4G. eIF4F functions as a capdependent RNA helicase that promotes the association of the mRNA with the 40S ribosomal subunit. The binding of MettRNA to the 40S ribosomal subunit is mediated by a ternary complex composed of eIF2-GTP-Met-tRNA (15). The release of eIFs is assisted by eIF5, which facilitates the hydrolysis of GTP carried out by eIF2. The GDP on eIF2 is exchanged for GTP by eIF2B in a regulated manner that is essential for ensuing rounds of initiation (29).Many types of stresses reduce global translation by triggering the phosphoryla...

Initiation is the rate-limiting step in protein synthesis and therefore an important target for regulation. For the initiation of translation of most cellular mRNAs, the cap structure at the 5 end is bound by the translation factor eukaryotic initiation factor 4E (eIF4E), while the poly(A) tail, at the 3 end, is recognized by the poly(A)-binding protein (PABP). eIF4G is a scaffold protein that brings together eIF4E and PABP, causing the circularization of the mRNA that is thought to be important for an efficient initiation of translation. Early in infection, rotaviruses take over the host translation machinery, causing a severe shutoff of cell protein synthesis. Rotavirus mRNAs lack a poly(A) tail but have instead a consensus sequence at their 3 ends that is bound by the viral nonstructural protein NSP3, which also interacts with eIF4GI, using the same region employed by PABP. It is widely believed that these interactions lead to the translation of rotaviral mRNAs, impairing at the same time the translation of cellular mRNAs. In this work, the expression of NSP3 in infected cells was knocked down using RNA interference. Unexpectedly, under these conditions the synthesis of viral proteins was not decreased, while the cellular protein synthesis was restored. Also, the yield of viral progeny increased, which correlated with an increased synthesis of viral RNA. Silencing the expression of eIF4GI further confirmed that the interaction between eIF4GI and NSP3 is not required for viral protein synthesis. These results indicate that NSP3 is neither required for the translation of viral mRNAs nor essential for virus replication in cell culture.

As intracellular parasites, viruses require a host cell in order to replicate. However, they face a series of cellular responses against infection. One of these responses is the activation of the double-stranded RNA (dsRNA)-activated protein kinase R (PKR). PKR phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), which in turn results in global protein synthesis inhibition and formation of stress granules (SGs). Recent studies have shown that SGs can interfere with the replicative cycle of certain viruses. This review addresses how viruses have evolved different control strategies at the SG level to ensure an efficient replication cycle during the cellular stress response triggered by the viral infection.

Translation is a complex process involving diverse cellular proteins, including the translation initiation factor eIF4E, which has been shown to be a protein that is a point for translational regulation. Viruses require components from the host cell to complete their replication cycles. Various studies show how eIF4E and its regulatory cellular proteins are manipulated during viral infections. Interestingly, viral action mechanisms in eIF4E are diverse and have an impact not only on viral protein synthesis, but also on other aspects that are important for the replication cycle, such as the proliferation of infected cells and stimulation of viral reactivation. This review shows how some viruses use eIF4E and its regulatory proteins for their own benefit in order to spread themselves.

SARS-CoV-2 has rapidly generated a pandemic. Vaccines are currently being rolled out to control the viral spread and prevent deaths. Emergency vaccines, using new platforms, have been approved. Their effectiveness, safety and immunogenicity in different populations are not fully known. This study aimed to discover the immunogenicity of the messenger ribonucleic acid (mRNA) BNT162b2 and adenovirus vector Ad5-nCoV vaccines through IgG antibody generation against subunit 1 of protein S (S1 IgG) and assess the side effects of the vaccines. A total of 115 vaccinated people were included, 61 of whom received the BNT162b2 vaccine, while 54 received Ad5-nCoV. Measurements of S1 IgG antibodies were carried out using the enzyme-linked immunosorbent assay (ELISA) technique. The BNT162b2 vaccine generated S1 IgG antibodies in 80.3% of the participants after the first dose. The number of seropositive participants increased to 98.36% with the administration of the second dose. The Ad5-nCoV vaccine generated S1 IgG antibodies in 88.89% of those vaccinated. Women generated more antibodies when administered either vaccine. There were no serious adverse effects from vaccination. In conclusion, not all participants had detectable S1 IgG antibodies. The Ad5-nCoV vaccine presented the most seronegative cases. The studied vaccines were shown to be safe.