Dengue and Zika Virus Dynamics in Monkeys

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Questions and Answers

What an animal was identified as a novel host for the pathogens discussed?

Syrian hamster

Cynomolgus macaque

African green monkey

Neotropical squirrel monkey (correct)

What is the primary mechanism through which pathogens are typically cleared from the body?

Immune response (correct)

Antiviral drugs

Vaccination

Bacterial intervention

Which mosquito species is indicated as having been involved in the delivery of viruses to the monkey hosts?

Aedes aegypti

Culex pipiens

Aedes africanus (correct)

Anopheles gambiae

What disease was first isolated in Uganda from a febrile sentinel monkey?

Zika virus (B) Signup and view all the answers

What factor is suggested to influence the transmission of sylvatic viruses in the study?

Viral replication and immune clearance (D) Signup and view all the answers

What type of relationship was observed in studies regarding infection magnitude and duration?

Inverse relationship (B) Signup and view all the answers

How was the virus delivered to the hosts in the majority of previous studies?

Needle injection (D) Signup and view all the answers

Which of the following vaccination methods was not mentioned in the context of the study?

Subunit vaccination (B) Signup and view all the answers

What strategy showed higher rates of persistence in both host and vector populations?

Tortoise strategy (C) Signup and view all the answers

What was the main focus of Ben-Shachar and Koelle's investigation?

Replication-clearance trade-off in DENV (B) Signup and view all the answers

What species of mosquitoes were used to monitor transmission in the current study?

Ae. albopictus (D) Signup and view all the answers

What treatment group did the macaque with ID NV289 belong to?

Control (C) Signup and view all the answers

How many infected mosquitoes were used in the high dose treatment for DENV?

10 (B) Signup and view all the answers

What immune response was invoked to explain the replication-clearance trade-off?

Natural killer (NK) cells (B) Signup and view all the answers

What was the purpose of the Bonferroni correction mentioned in the content?

To account for multiple comparisons (A) Signup and view all the answers

What type of data was primarily used to test the study's hypotheses?

Within-host simulation models (C) Signup and view all the answers

What were the two viral strains used to infect the squirrel monkeys?

DENV-2 and sylvatic African ZIKV (C) Signup and view all the answers

What was measured to evaluate the neutralizing antibody response post-treatment?

PRNT80 (D) Signup and view all the answers

Which parameter indicates the number of mosquitoes with detectable virus in their saliva?

No. infected mosquitoes with detectable virus (A) Signup and view all the answers

Which of the following was NOT measured in the study?

Heart rate (A) Signup and view all the answers

What was the size of the cohorts of monkeys used for the different infections?

10 monkeys for DENV and 10 for ZIKV (B) Signup and view all the answers

How many infected mosquitoes were used for the high dose treatment of ZIKV?

15 (C) Signup and view all the answers

What is indicated by the peak titer in the context of the study?

The peak concentration of virus in serum (C) Signup and view all the answers

What does PRNT stand for?

Plaque Reduction Neutralization Test (C) Signup and view all the answers

What was the primary purpose of measuring neutralizing antibody levels in the macaques?

To assess seroconversion and immune response (C) Signup and view all the answers

Which macaque did not seroconvert despite receiving a mosquito bite with detectable virus?

BC407 (C) Signup and view all the answers

What statistical measure was primarily used for analyzing neutralizing antibody levels?

PRNT80 values (C) Signup and view all the answers

What differentiates the monitoring of macaques from squirrel monkeys in the experiment?

Squirrel monkeys underwent necropsies while macaques did not. (D) Signup and view all the answers

What condition was observed in macaque SB393 regarding mosquito saliva?

It was bitten by a mosquito that did not salivate. (B) Signup and view all the answers

How many macaques were reassigned to the control treatment after initial analysis?

Only one macaque (D) Signup and view all the answers

What was a significant factor for the increased sample size during mosquito feeding on ZIKV-infected macaques?

It aimed to ensure adequate representation in experiments. (D) Signup and view all the answers

What was the reason stool samples were not collected from squirrel monkeys?

Squirrel monkeys were housed in pairs. (B) Signup and view all the answers

What concern arose when ZIKV was detected in the Americas in 2015?

The potential for a neotropical sylvatic cycle. (D) Signup and view all the answers

What was the primary putative native host for ZIKV in the study?

Cynomolgus macaque (A) Signup and view all the answers

What percentage of wild cynomolgus macaques in Malaysia tested seropositive for DENV?

≥ 50% (A) Signup and view all the answers

What role do mathematical models play in studies of arbovirus transmission?

They help predict between-host transmission and spillover events. (B) Signup and view all the answers

Which statement about ZIKV in Asia is supported by the content?

Human ZIKV infections are scarce in Asia, suggesting the possibility of spillover. (A) Signup and view all the answers

What is unclear regarding the potential spillback events mentioned in the study?

Whether ZIKV can create new sylvatic cycles. (D) Signup and view all the answers

What do host risk assessments indicate about cynomolgus macaques?

They have the highest risk of hosting ZIKV among primate species. (D) Signup and view all the answers

What trade-off is considered crucial in mathematical models predicting viral transmission?

Instantaneous pathogen transmission and infection duration. (A) Signup and view all the answers

What was the association between the dose of DENV-2 delivered and the likelihood of squirrel monkeys becoming detectably viremic?

Doses had no significant impact on viremia likelihood (C) Signup and view all the answers

What percentage of macaques experienced seroconversion after being delivered sylvatic ZIKV via mosquito bite?

100% (A) Signup and view all the answers

What was the relationship predicted by Hypothesis 2 regarding NK cells and peak virus titer?

NK cells would show a negative relationship with peak virus titer (B) Signup and view all the answers

What was the minimum mean harmonic PRNT80 reported in the study?

320 (B) Signup and view all the answers

How many of the intrathoracially inoculated mosquitoes that fed on macaques had detectable ZIKV in their saliva?

58/70 (A) Signup and view all the answers

What was the correlation between the number of mosquitoes salivating ZIKV and the total dose delivered?

Tight positive correlation (B) Signup and view all the answers

What was the relationship between NK cells and neutralizing antibody titers reported on day 1 after infection?

Higher NK cell counts associated with lower neutralizing antibody titers (B) Signup and view all the answers

How many squirrel monkeys showed detectable DENV-2 in mosquito saliva at 3 and 4 days post-infection?

Not detectable in any salivations (D) Signup and view all the answers

Study Notes

Trade-offs Shaping Transmission of Sylvatic Dengue and Zika Viruses in Monkey Hosts

Sylvatic dengue (DENV) and Zika (ZIKV) viruses originate in Old World sylvatic cycles involving monkeys and canopy-living mosquitoes.
These viruses have spilled over to human populations and been translocated to the Americas, potentially leading to spillback into Neotropical sylvatic cycles.
Studies of the trade-offs influencing within-host dynamics and transmission of these viruses are lacking, hindering predictions of spillover/spillback.
Researchers infected cynomolgus macaques (Asian) and squirrel monkeys (American) with sylvatic strains of DENV-2 or ZIKV via mosquito bites.
Viral replication (viremia), immune responses (NK cells, neutralizing antibodies), and transmission to mosquitoes were monitored.
ZIKV achieved high titers, translating to high mosquito transmission in both hosts.
DENV-2 replication was lower, and transmission only occurred when serum viremia was near the detection limit.
The study found evidence of an immunologically mediated trade-off between viral replication duration and magnitude.
ZIKV's higher peak titers were associated with shorter viremia durations, and higher NK cell levels correlated with lower peak ZIKV titers and reduced DENV-2 antibody levels.
Neotropical monkey transmission patterns suggest ZIKV has greater potential for establishing a sylvatic transmission cycle in the Americas than DENV-2.

Experimental Design

Cynomolgus macaques (native host) were infected with DENV-2 (strain P8-1407) and ZIKV (strain DakAR 41525).
Squirrel monkeys (novel host) were also infected with DENV-2 and ZIKV.
Monkeys received either low (1 mosquito) or high (10 or 15 mosquitoes) doses of the infected mosquitoes.
Transmission to mosquitoes was monitored by observing subsequent infections in uninfected mosquitoes.
Viremia, NK cell levels, and neutralizing antibody titers (PRNTs) were analyzed.

Results and Sylvatic DENV-2 replication

DENV-2 replication was low, with viremia detected in only some monkeys.
Transmission to mosquitoes was observed only when serum viremia was near the detection limit.
The dose of DENV-2 did not significantly impact viremia or transmission.
Higher NK cells on day 1 were associated with lower neutralizing antibody titers in both macaque and squirrel monkey hosts.

Sylvatic ZIKV dynamics

ZIKV reached high titers and transmitted efficiently to mosquitoes in both macaques and squirrel monkeys.
ZIKV transmission was directly correlated with higher viral titers.
Compared to DENV-2, similar dissemination in both host species and a shorter duration of viremia was observed with ZIKV.

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Description

Explore the trade-offs in transmission and replication of sylvatic dengue and Zika viruses in monkey hosts. This quiz examines how these viruses interact within their hosts and their potential impacts on spillover into human populations. Test your understanding of the dynamics influencing these viral transmissions using data from recent research.