Biology subjects

Lopez-Lastra, M.

Publications and source records attributed to Lopez-Lastra, M..

3 recordsLinked to original sources

bioRxiv2026

DEAD-box RNA helicase DDX3X maintains the homeostasis of the Zika virus translation-replication cycle

DDX3X is a cellular DEAD-box ATP-dependent RNA helicase known to play pivotal roles during the replication cycle of different viruses including some flaviviruses. Whether DDX3X plays a role during replication of Zika virus (ZIKV), a mosquito-borne flavivirus with a broad tissue tropism, has not been explored in detail. Here, we show that DDX3X is required for efficient ZIKV replication in a human microglia cell line but no other cell lines. Mechanistically, we provide evidence showing that DDX3X is recruited to the viral replication compartments where it binds to the 5UTR of the ZIKV RNA and promotes viral protein synthesis in an ATP-dependent manner. We also show that DDX3X binds to the viral RNA-dependent RNA polymerase NS5 and interferes with viral RNA synthesis in an ATP-independent manner. Such an effect was not observed during replication of Dengue 2 virus in human microglia, revealing specific roles for DDX3X in the regulation of the translation-replication cycle of ZIKV in human microglia. IMPORTANCEZika virus emerged as a major threat to humans due to its pandemic potential and its association with birth defects and neurological complications. The lack of available vaccines or specific treatments makes the understanding of Zika virus-host interactions a priority. Here, we demonstrate a mechanism by which DDX3X, a cellular ATP-dependent RNA helicase, promotes Zika virus replication by regulating the translation-replication cycle in a human microglia cell line. Considering the threat of this virus to the human population and the wide range of RNA viruses that usurp this host protein to accomplish the replication cycle, DDX3X continuously rises as a potential and valuable target for pharmacological intervention.

microbiology↗

bioRxiv2025

Cell surface localization and intercellular transfer of the hantavirus nucleocapsid protein via a viral assembly-independent mechanism

Hantaviruses are segmented negative-sense RNA viruses that package their genome into helical ribonucleocapsids, by oligomerization of the nucleocapsid (N) protein along the viral RNA. Upon transmission to humans, hantaviruses can cause severe disease characterized by increased vascular permeability in the microvasculature, a key driver of pathogenesis. In patients and rodent reservoirs, robust and persistent antibody responses against the nucleocapsid (N) protein are consistently observed. Here we investigated whether the hantavirus N protein, described as a strictly intracellular protein, is released into the extracellular environment during viral infection. By using diverse experimental approaches, we demonstrate that in cells infected with Andes virus (ANDV) or the non-pathogenic Tula virus (TULV), the N protein localizes on the plasma membrane. Transfection experiments further revealed that the surface localization of N proteins from Murine, Arvicoline, Neotomine and Sigmodontine rodent-reservoir-associated hantaviruses did not require co-expression of other viral proteins indicating that its trafficking to the cell surface is mediated by a mechanism distinct from canonical virion assembly pathways. Moreover, we show that the N protein is secreted from cells into the extracellular milieu and is further transferred to neighboring cells. Interestingly, despite being present on the cell surface and secreted into the extracellular media, the TULV N protein transfer of the N protein to neighboring cells was significantly lower compared to that of ANDV N protein. The extracellular presence of hantavirus N proteins, and likely also from other clinically-relevant bunyaviruses, unveils new possible functions of the protein during the viral infection cycle, which is likely related to immune responses, immune modulation and viral pathogenesis.

microbiology↗

bioRxiv2018

Single nucleotide variant at the alphaVbeta3 integrin associated to Andes virus infection susceptibility.

BackgroundANDV, agent of hantavirus cardiopulmonary syndrome, enters through integrin cell protein. A change from leucine-to-proline at residues 33 in the PSI-domain (L33P) inhibits ANDV recognition. We assessed the association between this human-variant and ANDV infection.\n\nResultsWe defined susceptible genotype to \"TT\" (coding leucine) and protective \"CC\" (coding proline). TT was in 89.2% (66/74) of a first cohort of ANDV-cases and in 60% (63/105) of exposed close-household contacts who remained unifected (p<0.05). Protective genotype was absent in all 85 ANDV cases in both cohorts and was present at 11.4% in exposed close-household contacts who remained uninfected. Logistic regression modeling to become a case had an OR 6.2-12.6 (p<0.05) in presence of TT and ANDV well-known risk activities. Moreover, OR of 7.3 was obtained when TT condition was analyzed for two groups exposed to the same environmental risk.\n\nConclusionHost genetic background has an important role in ANDV-infection susceptibility in the studied population.\n\nAuthor summaryHantavirus is a worldwide infection known to cause two different diseases: the hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS or HPS), diseases seen in the old world and new world hantaviruses, respectively. Andes orthohantavirus (ANDV), is the etiological agent of HCPS in Chile and South of Argentina, and is the only hantavirus recognized to be transmited person-to-person. It has been suggested that {beta}3-integrin is a cellular receptor for ANDV entry into cells. Here we try to understand the role of one human genetic variant of {beta}3-integrin in susceptibility to ANDV-infection. We compared, exposed infected and non infected subjects, and their genotype differences regarding a {beta}3 integrin variant that change a Leucine to Proline at PSI domain of the receptor. Leucine and proline aminoacids at the PSI domain, turn the cell susceptible or resistant to ANDV-infection, respectively. We were able to show genotype differences in cases and close-household contact that suggest differences in ANDV-infection susceptibility. Our results propose that the TT genotype, that codes to leucine, is a risk factor to become infected with ANDV, and the CC genotype that codes for proline at PSI domain, is a protective factor. (193/200)

microbiology↗