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Editorial overview: Intraspecies transmission of viruses
Sander Herfst and Martin Ludlow
Current Opinion in Virology 2018, 28:v–vii
For a complete overview see the Issue
Available online 1st February 2018
https://doi.org/10.1016/j.coviro.2018.01.002
1879-6257/ã 2018 Elsevier B.V. All rights reserved.
Sander Herfst
Department of Viroscience, Erasmus Medical
Center, Wytemaweg 80, 3015 CN Rotterdam,
The Netherlands
e-mail: s.herfst@erasmusmc.nl
Sander Herfst is an Assistant Professor at the
Department of Viroscience of the Erasmus
Medical Center in Rotterdam, where he
works as workgroup leader of the respiratory
virus transmission group. He received a PhD
in Virology from the Erasmus University
Rotterdam. His research focuses on the
pathogenesis, virulence and transmissibility
of influenza A viruses, with special emphasis
on genetic and phenotypic viral factors
involved in the emergence of new
pandemics.
Martin Ludlow
University of Veterinary Medicine Hannover
Foundation, Research Center for Emerging
Infections and Zoonoses (RIZ), Bünteweg 17,
30559 Hannover, Germany
e-mail: martin.ludlow@tiho-hannover.de
Martin Ludlow is a group leader in Molecular
Virology at the Research Center for Emerging
Infections and Zoonoses in Hannover. He
received a BSc in Microbiology and a PhD in
Virology from Queen’s University Belfast. His
main research interests are focused on
identifying host and viral factors which
influence the pathogenesis and transmission
of orthopneumoviruses and animal
morbilliviruses.
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The intraspecies transmission of viruses is a complex and often poorly
understood phenomenon, but one which is critical to better understand as it
encompasses perhaps the most important part of the viral life cycle, namely
the routes through which a virus spreads from an infected to a susceptible
host. The acquisition of mutations by zoonotic viruses such as avian
influenza viruses which enable virus transmission via the respiratory route
in humans would have the potential to give rise to pandemics on relatively
short time scales of weeks and months. It is therefore vitally important to
investigate viral and host factors associated with virus transmission in order
to better inform the development of more effective epidemiological or
therapeutic intervention strategies. However, it can be challenging to design
experimental models which sufficiently replicate natural virus transmission
and characterization of virus particles in droplets or aerosols presents major
technical difficulties. Increasingly, the value of studying virus transmission
in natural experimental model systems is being recognized and is driving
major advances in our understanding of the associated mechanisms. Given
the uncertainty and environmental hazards encountered by a virus following
egress from an infected host, it is not surprising that viruses have evolved
strategies to maximize the chances of infecting a naive susceptible host. In
this issue of Current Opinion in Virology, researchers studying different
aspects of virus transmission present a synthesis of the current state of
knowledge of their respective field and where possible highlight knowledge
gaps and future research priorities.
The role of arthropod species as vectors mediating transmission of viruses
between humans (arboviruses), has been exhaustively explored since
the late 1800s when the link between mosquitos and the spread of yellow
fever was first proposed and eventually experimentally confirmed. How-
ever, major knowledge gaps still exist in relation to which arboviruses
pose a direct threat to human populations. Marietjie Venter helps to more
clearly define this risk by providing a comprehensive overview of zoonotic
African arboviruses. This is an especially timely review given the recent
emergence of one arbovirus, Zika virus, in the Americas following ex-
tensive spread in Asia and many Pacific Islands. The spread of viruses via
arthropod vectors does not only affect animals but also members of the
kingdom Plantae. This interesting and more recent field of research is
summarized by Wei et al. who describe how some plant viruses are
horizontally disseminated by insect species and vertically transmitted
to insect offspring. Either mode of virus transmission is dependent on
these persistently propagated viruses having to successfully navigate
multiple tissue and membrane barriers within the insect host to spread
to the salivary gland or female ovary.
The study of virus populations within and between hosts is a subject of
increasing interest in virology as heterogenicity of viral genomes can lead to
new properties such as immune evasion, host switching and escape from
antivirals. In the first of two reviews on this subject, McCrone and Lauring
outline how transmission events have a major role in shaping the diversity of
virus populations via genetic bottlenecks. A variety of approaches to
Current Opinion in Virology 2018, 48:v–vii
vi Emerging viruses: intraspecies transmission
measure such bottlenecks using experimental and natural
models are discussed together with determinants which
modulate this process. Finally, the consequences of bot-
tlenecks during virus transmission chains for the long-
term evolution of a virus are outlined. This study is
complemented by a review by Theys et al. who examine
the impact of within host evolution of HIV-1 on trans-
mission dynamics. It is well established that there is a
discrepancy between the within host evolution rates of
HIV-1 and the corresponding value for between host
evolution rates with ancestral donor viruses preferentially
transmitted to susceptible hosts. Viral and host factors
underlying these differences are highlighted together
with the consequences of within host evolution for suc-
cessful transmission events and implications for thera-
peutic intervention strategies such as pre-exposure
prophylaxis.
A better understanding of the complexity of virus trans-
mission in reservoir host species is clearly required to
improve epidemiological models and better predict the
emergence of novel zoonotic viruses. However, the sus-
tained transmission of many viruses including avian influ-
enza viruses, animal morbilliviruses, and foot and mouth
disease virus, within an ecosystem often relies on spread
within and between members of multiple host species
with periodic sustained transmission in one species some-
times resulting in pandemics or epizootics if the right
balance of ecological, epidemiological and host suscepti-
bility factors are present. Thus, for many viruses the
artificial human constructs of intra-species and inter-spe-
cies virus transmission often operate in tandem in differ-
ent co-circulating transmission chains in nature. In most
cases these use the same molecular mechanisms to initi-
ate infection and routes of transmission to spread to the
next susceptible host. The following six review articles
collectively highlight various aspects of the complexity of
virus transmission in reservoir or spillover species.
Members of the Rodentia, Eulipotyphla and Chiroptera
comprise the reservoir for hantaviruses, with shedding
of these viruses from rodents into the environment result-
ing in spillover to non-reservoir host species including
humans. Humans presumably become infected following
inhalation of or direct contact with infectious virus pres-
ent in wildlife host excreta and saliva. Forbes et al.
describe the recent advances in our understanding of
shedding kinetics in wild rodent populations, heteroge-
neity in transmission dynamics and occupational, recrea-
tional and environmental risk factors for zoonotic infec-
tions. Unfortunately, gaps in our understanding of
hantavirus transmission in non-rodent species remain.
A more complete understanding of the maintenance
and transmission of hantaviruses within reservoir host
populations is critical to develop more effective interven-
tion strategies necessary to mitigate and prevent human
infections.
Current Opinion in Virology 2018, 48:v–vii
The modes of transmission of Henipaviruses such as
Hendra or Nipah virus, which pose a clear threat to
human populations, are covered by Weatherman et al.
Virus transmission between the reservoir Pteropid bat
species is assumed to be via close contact in high popula-
tion density roosts with urine suspected to be main route
through virus spreads between individuals. Transmission
of Hendra virus between horses appears to be relatively
inefficient, contrasting with clear evidence for efficient
spread of Nipah virus between pigs via direct contact with
nasal secretions. Whereas no evidence for human to
human spread of Hendra virus is available, Nipah virus
is representative of a zoonotic virus on the cusp of
intraspecies transmission as limited chains of transmission
in humans have been reported in small outbreaks in India
and Bangladesh.
The fascinating conundrum of rabies virus which con-
trasts with all other lyssaviruses with respect to host
specificity is explored by Marston et al. Although spillover
events of bat lyssaviruses into many species is relatively
common, especially in North America, actual host switch-
ing events are very rare. Rabies virus represents an
exception to this rule with multiple lineages circulating
in different animal species. The authors propose that
rabies virus is ‘pre-adapted’ to cross-species infections,
negating the necessity for causal mutations but possible
molecular mechanisms underlying such events are dis-
cussed including recombination events and virus subpop-
ulation heterogeneity.
Wild birds form the natural reservoir of avian influenza
viruses, but the prevalence and subtype distribution
differ between and across bird taxa. The efficiency of
transmission between and within different host taxa
depends on the availability and exposure of susceptible
hosts. Van Dijk et al. summarize how these epidemiologi-
cal determinants may be cumulatively affected by key
host traits such as migration, age, pre-existing immunity,
and virus traits such as virus binding and replication.
Importantly, the authors identify many aspects of the
epidemiology of this virus group that have not yet been
assessed and suggest improvements in experimental
approaches to better address these knowledge gaps.
Differences in genome size between single host ortho-
poxviruses such as Variola or camelpox virus and multiple
host orthopoxviruses such as cowpox virus or monkeypox
viruses are described by Reynolds et al. who provide an
evolutionary framework in which to better understand the
consequences of the loss of assumed host range genes. It
is assumed that this loss of specific genes in combination
with other ecological factors such as population size of the
host species, leads to sustained intraspecies transmission
in the absence of interspecies transmission. The absence
of well described reservoir hosts for many orthopoxviruses
and the discovery of so called ‘cryptic’ orthopoxviruses for
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which very little information is available, necessitates
more extensive sampling of wildlife especially in areas
of the world which have been poorly sampled for this
virus family.
The complexity of virus transmission is also highlighted
by Joe et al., who show that marine morbilliviruses such as
cetacean morbillivirus and phocine distemper virus can
infect multiple related species of cetaceans and pinnipeds
respectively, in some instances giving rise to large epizoo-
tics as a result of sustained intraspecies virus transmission.
The differential clinical disease spectrum observed follow-
ing morbillivirus infection of marine mammals is presum-
ably due to differences in expression of host factors which
serve to restrict virus infections. The spread of a terrestrial
morbillivirus, canine distemper virus, into the marine
environment is also discussed. This resulted in two large
epizootics in seals in Lake Baikal and the Caspian Sea,
many details of which are still poorly understood.
The final two review articles cover perhaps the most
fundamental aspect of virus transmission, the routes
through which a virus spreads to infect a susceptible host,
thus continuing the chain of transmission. An overview of
the complexities and uncertainties of foot and mouth
disease virus (FMDV) transmission is provided by
Paton et al. who discuss virus transmission from the level
of individual animals to mechanisms of cross-regional
virus spread. The use of experimental models of virus
transmission is presented together with the difficulties
inherent in trying to model endemic virus spread or the
explosive epizootics which can occur when FMDV by a
chance event spreads to an FMDV free region. A way
forward using large scale next generation sequencing of
historical FMDV outbreaks is presented. This enables
the reconstruction of transmission chains using viral phy-
lodynamics, thus allowing the construction of better
epidemiological models, which are crucial for designing
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Editorial overview Herfst and Ludlow vii
intervention strategies to control and stop such FMDV
outbreaks. Finally, Kutter et al. provide a comprehensive
overview of the primary mechanisms of virus spread
utilized by human viruses which are transmitted via
the respiratory route of infection. This is based on a
careful analysis of the available literature on experimental
and observational clinical studies on inter-human virus
spread via contact, droplets or aerosols. A paucity of
knowledge in many aspects of virus transmission is dis-
cussed, together with recommendations for how to bridge
this gap via the use of increasingly sophisticated experi-
mental systems. Importantly, they highlight inconsisten-
cies into how the available knowledge in this field is
translated into national guidelines for infection.
Future advances in understanding intraspecies virus
transmission will be dependent upon the same techno-
logical advances in genomics and animal modeling which
is driving progress in many areas of virology. The rapidly
expanding and increasingly sophisticated field of viral
phylodynamics in conjunction with an increasing avail-
ability of whole genome sequences from clinical samples
is revolutionizing our ability to trace the evolution of
pandemic outbreaks of viral disease in real time. This is
complemented by the rapid increase of annotated whole
genome sequences from many animal species and the
rapidly decreasing costs of gene synthesis, which collec-
tively open new avenues to investigate host factors which
influence virus transmission in a wider array of species
than was previously possible. Mechanistic studies into
key host determinants of virus transmission such as
cellular receptors or innate immune response molecules
will complement the use of increasingly sophisticated
natural model systems of virus infection and transmission
in which recombinant viruses based on clinical isolates are
used to explore and illuminate aspects of the underlying
virus pathogenesis underpinning the routes of virus
transmission.
Current Opinion in Virology 2018, 48:v–vii