Biology subjects

Delima, G. K.

Publications and source records attributed to Delima, G. K..

3 recordsLinked to original sources

bioRxiv2022

Influenza A virus coinfection dynamics are shaped by distinct virus-virus interactions within and between cells

When multiple viral populations propagate within the same host environment, they often shape each others dynamics. These interactions can be positive or negative and can occur at multiple scales, from coinfection of a cell to co-circulation at a global population level. For influenza A viruses (IAVs), the delivery of multiple viral genomes to a cell substantially increases burst size. However, despite its relevance for IAV evolution through reassortment, the implications of this positive density dependence for coinfection between distinct IAVs has not been explored. Furthermore, the extent to which these interactions within the cell shape viral dynamics at the level of the host remains unclear. Here we show that, within cells, coinfecting IAVs strongly augment the replication of a focal strain, irrespective of the native host of the coinfecting IAV or its homology to the focal strain. Coinfecting viruses with a low intrinsic reliance on multiple infection offer the greatest benefit. Nevertheless, virus-virus interactions at the level of the whole host are antagonistic. This antagonism is recapitulated in cell culture when the coinfecting virus is introduced several hours prior to the focal strain or under conditions conducive to multiple rounds of viral replication. Together, these data suggest that beneficial virus-virus interactions within cells are counterbalanced by competition for susceptible cells during viral propagation through a tissue. The integration of virus-virus interactions across scales is critical in defining the outcomes of viral coinfection.

microbiology↗

bioRxiv2021

Timing of exposure is critical in a highly sensitive model of SARS-CoV-2 transmission

Transmission efficiency is a critical factor determining the size of an outbreak of infectious disease. Indeed, the propensity of SARS-CoV-2 to transmit among humans precipitated and continues to sustain the COVID-19 pandemic. Nevertheless, the number of new cases among contacts is highly variable and underlying reasons for wide-ranging transmission outcomes remain unclear. Here, we evaluated viral spread in golden Syrian hamsters to define the impact of temporal and environmental conditions on the efficiency of SARS-CoV-2 transmission through the air. Our data show that exposure periods as brief as one hour are sufficient to support robust transmission. However, the timing after infection is critical for transmission success, with the highest frequency of transmission to contacts occurring at times of peak viral load in the donor animals. Relative humidity and temperature had no detectable impact on transmission when exposures were carried out with optimal timing. However, contrary to expectation, trends observed with sub-optimal exposure timing suggest improved transmission at high relative humidity or high temperature. In sum, among the conditions tested, our data reveal the timing of exposure to be the strongest determinant of SARS-CoV-2 transmission success and implicate viral load as an important driver of transmission.

microbiology↗

bioRxiv2019

Dysregulation of M segment gene expression contributes to influenza A virus host restriction

The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate the genetic contributions of the M segment to host adaptation, and the underlying mechanisms, we examined a panel of isogenic viruses that carry avian- or human-derived M segments. Avian, but not human, M segments restricted viral growth and transmission in mammalian model systems, and the restricted growth correlated with increased expression of M2 relative to M1. M2 overexpression was associated with intracellular accumulation of autophagosomes, which was alleviated by interference of the viral proton channel activity by amantadine treatment. As M1 and M2 are expressed from the M mRNA through alternative splicing, we separated synonymous and non-synonymous changes that differentiate human and avian M segments and found that dysregulation of gene expression leading to M2 overexpression diminished replication, irrespective of amino acid composition of M1 or M2. Moreover, in spite of efficient replication, virus possessing a human M segment that expressed avian M2 protein at low level did not transmit efficiently. We conclude that (i) determinants of transmission reside in the IAV M2 protein, and that (ii) control of M segment gene expression is a critical aspect of IAV host adaptation needed to prevent M2-mediated dysregulation of vesicular homeostasis.\n\nAuthor summaryInfluenza A virus (IAV) pandemics arise when a virus adapted to a non-human host overcomes species barriers to successfully infect humans and sustain human-to-human transmission. To gauge the adaptive potential and therefore pandemic risk posed by a particular IAV, it is critical to understand the mechanisms underlying viral adaptation to human hosts. Here, we focused on the role of one of IAVs eight gene segments, the M segment, in host adaptation. Comparing the growth of IAVs with avian- and human-derived M segments in avian and mammalian systems revealed that the avian M segment restricts viral growth specifically in mammalian cells. We show that the mechanism underlying this host range phenotype is a dysregulation of viral gene expression when the avian IAV M segment is transcribed in mammalian cells. In particular, excess production of the M2 protein results in viral interference with cellular functions on which the virus relies. Our results therefore reveal that the use of cellular machinery to control viral gene expression leaves the virus vulnerable to over- or under-production of critical viral gene products in a new host species.

microbiology↗