The genetic basis of viral virulence

The precise genetic and molecular determ inants of viral virulence are poorly understood. Genetic studies with influenza and reovirus have indicated that virulence is multigenic. The high frequency of m utation of RNA viruses can complicate genetic analyses of virulence, resulting in phenotypes that are difficult to interpret. The ease with which the reoviruses reassort genome segments has made it possible to isolate reassortants from parental viruses causing different patterns of anim al disease. It has thus been feasible to show that each of the three outer capsid proteins plays a m ajor role in the pathogenesis of anim al infection: the viral haem agglutinin determines the specificity of the im mune response and cell and tissue tropism ; the p ic protein plays a central role in determ ining yield at portals of entry as well as in differentiated tissues; the δ3 protein inhibits host m acrom olecular synthesis. Thus virulence is clearly multigenic, with each of the viral components playing distinct roles.

1996 ◽  
Vol 70 (8) ◽  
pp. 4877-4883 ◽  
Author(s):  
M C Ruiz ◽  
A Charpilienne ◽  
F Liprandi ◽  
R Gajardo ◽  
F Michelangeli ◽  
...  
Keyword(s):  

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 959
Author(s):  
Celeste M. Donato ◽  
Julie E. Bines

Group A rotaviruses belong to the Reoviridae virus family and are classified into G and P genotypes based on the outer capsid proteins VP7 and VP4, respectively [...]


2020 ◽  
Author(s):  
Stephanie Gummersheimer ◽  
Pranav Danthi

ABSTRACTThe capsids of mammalian reovirus contain two concentric protein shells, the core and the outer capsid. The outer capsid is comprised of µ1-σ3 heterohexamers which surround the core. The core is comprised of λ1 decamers held in place by σ2. After entry into the endosome, σ3 is proteolytically degraded and µ1 is cleaved and exposed to form ISVPs. ISVPs undergo further conformational changes to form ISVP*s, resulting in the release of µ1 peptides which facilitate the penetration of the endosomal membrane to release transcriptionally active core particles into the cytoplasm. Previous work has identified regions or specific residues within reovirus outer capsid that impact the efficiency of cell entry. We examined the functions of the core proteins λ1 and σ2. We generated a reovirus T3D reassortant that carries strain T1L derived σ2 and λ1 proteins (T3D/T1L L3S2). This virus displays a lower ISVP stability and therefore converts to ISVP*s more readily. To identify the basis for lability of T3D/T1L L3S2, we screened for hyper-stable mutants of T3D/T1L L3S2 and identified three point mutations in µ1 that stabilize ISVPs. Two of these mutations are located in the C-terminal ϕ region of µ1, which has not previously been implicated in controlling ISVP stability. Independent from compromised ISVP stability, we also found that T3D/T1L L3S2 launches replication more efficiently and produces higher yields in infected cells. In addition to identifying a new role for the core proteins in disassembly events, these data highlight that core proteins may influence multiple stages of infection.IMPORTANCEProtein shells of viruses (capsids) have evolved to undergo specific changes to ensure the timely delivery of genetic material to host cells. The 2-layer capsid of reovirus provides a model system to study the interactions between capsid proteins and the changes they undergo during entry. We tested a virus in which the core proteins were derived from a different strain than the outer capsid. We found that this mismatched virus was less stable and completed conformational changes required for entry prematurely. Capsid stability was restored by introduction of specific changes to the outer capsid, indicating that an optimal fit between inner and outer shells maintains capsid function. Separate from this property, mismatch between these protein layers also impacted the capacity of virus to initiate infection and produce progeny. This study reveals new insights into the roles of capsid proteins and their multiple functions during viral replication.


mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Ignacio de la Higuera ◽  
George W. Kasun ◽  
Ellis L. Torrance ◽  
Alyssa A. Pratt ◽  
Amberlee Maluenda ◽  
...  

ABSTRACT The discovery of cruciviruses revealed the most explicit example of a common protein homologue between DNA and RNA viruses to date. Cruciviruses are a novel group of circular Rep-encoding single-stranded DNA (ssDNA) (CRESS-DNA) viruses that encode capsid proteins that are most closely related to those encoded by RNA viruses in the family Tombusviridae. The apparent chimeric nature of the two core proteins encoded by crucivirus genomes suggests horizontal gene transfer of capsid genes between DNA and RNA viruses. Here, we identified and characterized 451 new crucivirus genomes and 10 capsid-encoding circular genetic elements through de novo assembly and mining of metagenomic data. These genomes are highly diverse, as demonstrated by sequence comparisons and phylogenetic analysis of subsets of the protein sequences they encode. Most of the variation is reflected in the replication-associated protein (Rep) sequences, and much of the sequence diversity appears to be due to recombination. Our results suggest that recombination tends to occur more frequently among groups of cruciviruses with relatively similar capsid proteins and that the exchange of Rep protein domains between cruciviruses is rarer than intergenic recombination. Additionally, we suggest members of the stramenopiles/alveolates/Rhizaria supergroup as possible crucivirus hosts. Altogether, we provide a comprehensive and descriptive characterization of cruciviruses. IMPORTANCE Viruses are the most abundant biological entities on Earth. In addition to their impact on animal and plant health, viruses have important roles in ecosystem dynamics as well as in the evolution of the biosphere. Circular Rep-encoding single-stranded (CRESS) DNA viruses are ubiquitous in nature, many are agriculturally important, and they appear to have multiple origins from prokaryotic plasmids. A subset of CRESS-DNA viruses, the cruciviruses, have homologues of capsid proteins encoded by RNA viruses. The genetic structure of cruciviruses attests to the transfer of capsid genes between disparate groups of viruses. However, the evolutionary history of cruciviruses is still unclear. By collecting and analyzing cruciviral sequence data, we provide a deeper insight into the evolutionary intricacies of cruciviruses. Our results reveal an unexpected diversity of this virus group, with frequent recombination as an important determinant of variability.


2019 ◽  
Vol 286 (1895) ◽  
pp. 20182452 ◽  
Author(s):  
Emily J. Remnant ◽  
Niklas Mather ◽  
Thomas L. Gillard ◽  
Boris Yagound ◽  
Madeleine Beekman

The arrival of the ectoparasitic mite Varroa destructor on the western honeybee Apis mellifera saw a change in the diversity and prevalence of honeybee RNA viruses. One virus in particular, deformed wing virus (DWV) has become closely associated with V. destructor , leading many to conclude that V. destructor has affected viral virulence by changing the mode of transmission. While DWV is normally transmitted via feeding and faeces, V. destructor transmits viruses by direct injection. This change could have resulted in higher viral prevalence causing increased damage to the bees. Here we test the effect of a change in the mode of transmission on the composition and levels of honeybee RNA viruses in the absence of V. destructor . We find a rapid increase in levels of two viruses, sacbrood virus (SBV) and black queen cell virus (BQCV) after direct injection of viral extracts into honeybee pupae. In pupae injected with high levels of DWV extracted from symptomatic adult bees, DWV levels rapidly decline in the presence of SBV and BQCV. Further, we observe high mortality in honeybee pupae when injected with SBV and BQCV, whereas injecting pupae with high levels of DWV results in near 100% survival. Our results suggest a different explanation for the observed association between V. destructor and DWV. Instead of V. destructor causing an increase in DWV virulence, we hypothesize that direct virus inoculation, such as that mediated by a vector, quickly eliminates the most virulent honeybee viruses resulting in an association with less virulent viruses such as DWV.


2002 ◽  
Vol 59 (7) ◽  
pp. 1229-1234 ◽  
Author(s):  
Paul D.N Hebert ◽  
Melania E.A Cristescu

Using freshwater cladocerans as an example, this paper explores the contributions that genetic analyses are making to the field of invasion biology. Most importantly, this approach enables a quantification of the incidence of both recent and past invasions. By determining genetic divergence between European and North American lineages of cladocerans, it is possible to estimate the natural incidence of past exchange between these continents. The results of this analysis establish that the current pace of species invasions is extraordinary; present rates are nearly 50 000 times higher than historical levels. Genetic studies can also exploit molecular markers to localize the points of origin of invaders. Finally, genetic studies are poised to play an important role in monitoring invasions; the DNA bar-coding of life is now simple and rapid enough to enable the development of molecular identification systems.


Vaccine ◽  
2009 ◽  
Vol 27 (33) ◽  
pp. 4434-4438 ◽  
Author(s):  
Alan J. Guthrie ◽  
Melvyn Quan ◽  
Carina W. Lourens ◽  
Jean-Christophe Audonnet ◽  
Jules M. Minke ◽  
...  

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