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1. Modeling the Effects of Morphine-Altered Virus Specific Antibody Responses on HIV/SIV Dynamics

   https://doi.org/10.1038/s41598-019-41751-8  

   Mutua, Jones M. ; Perelson, Alan S. ; Kumar, Anil ; Vaidya, Naveen K. ( April 2019 , Scientific Reports)

   Drugs of abuse, such as opiates, have been widely associated with enhancing HIV replication, accelerating disease progression and diminishing host-immune responses, thereby making it harder to effectively manage HIV infection. It is thus important to study the effects of drugs of abuse on HIV-infection and immune responses. Here, we develop mathematical models that incorporate the effects of morphine-altered antibody responses on HIV/SIV dynamics. Based on fitting the model to experimental data from simian immunodeficiency virus (SIV) infections in control and morphine-addicted macaques, we found that two of the most significant effects of virus specific antibodies are neutralizing viral particles and enhancing viral clearance. Using our model, we quantified how morphine alters virus-specific antibody responses, and how this alteration affects the key components of virus dynamics such as infection rate, virus clearance, viral load, CD4⁺T cell count, and CD4⁺T cell loss in SIV-infected macaques under conditioning with morphine. We found that in a subpopulation of SIV-infected morphine addicted macaques, the presence of drugs of abuse may cause significantly diminished antibody responses, resulting in more severe infection with increased SIV infectivity, a decreased viral clearance rate, increased viral load, and higher CD4⁺T cell loss.
2. The Effect of Phenoloxidase Activity on Survival Is Host Plant Dependent in Virus-Infected Caterpillars

   https://doi.org/10.1093/jisesa/ieaa116  

   Resnik, Justine L ; Smilanich, Angela M ( September 2020 , Journal of Insect Science)

   Jaronski, Stefan (Ed.)

   Abstract An important goal of disease ecology is to understand trophic interactions influencing the host–pathogen relationship. This study focused on the effects of diet and immunity on the outcome of viral infection for the polyphagous butterfly, Vanessa cardui Linnaeus (Lepidoptera: Nymphalidae) (painted lady). Specifically, we aimed to understand the role that larval host plants play when fighting a viral pathogen. Larvae were orally inoculated with the entomopathogenic virus, Junonia coenia densovirus (JcDV) (Family Parvoviridae, subfamily Densovirinae, genus Protoambidensovirus, species Lepidopteran protoambidensovirus 1) and reared on two different host plants (Lupinus albifrons Bentham (Fabales: Fabaceae) or Plantago lanceolata Linnaeus (Lamiales: Plantaginaceae)). Following viral infection, the immune response (i.e., phenoloxidase [PO] activity), survival to adulthood, and viral load were measured for individuals on each host plant. We found that the interaction between the immune response and survival of the viral infection was host plant dependent. The likelihood of survival was lowest for infected larvae exhibiting suppressed PO activity and feeding on P. lanceolata, providing some evidence that PO activity may be an important defense against viral infection. However, for individuals reared on L. albifrons, the viral infection had a negligible effect on the immune response, and these individuals also had higher survivalmore »and lower viral load when infected with the pathogen compared to the controls. Therefore, we suggest that host plant modifies the effects of JcDV infection and influences caterpillars’ response when infected with the virus. Overall, we conclude that the outcome of viral infection is highly dependent upon diet, and that certain host plants can provide protection from pathogens regardless of immunity.« less
3. Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription

   https://doi.org/10.1128/JVI.00279-17  

   Ke, Qi ; Weaver, Wade ; Pore, Adam ; Gorgoglione, Bartolomeo ; Wildschutte, Julia Halo ; Xiao, Peng ; Shepherd, Brian S. ; Spear, Allyn ; Malathi, Krishnamurthy ; Stepien, Carol A. ; et al ( July 2017 , Journal of Virology)

   Viral Hemorrhagic Septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the northern hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral genes expression. By systematically screening each of the six VHSV structural and nonstructural genes, we have identified matrix protein (M) as its most potent anti-host protein. VHSV-IVb M alone suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner. M also suppressed the constitutively active SV40 promoter and globally decreased cellular RNA levels. Chromatin immunoprecipitation (ChIP) studies illustrated that M inhibited RNA polymerase II (RNAP II) recruitment to gene promoters, and decreased RNAP II CTD Ser2 phosphorylation during VHSV infection. However, transcription directed by RNAP I-III was suppressed by M. To identify regions of functional importance, M proteins from a variety of VHSV strains were tested in cell-based transcriptional inhibition assays. M protein of a particular VHSV-Ia strain, F1, was significantly less potent than -IVb M at inhibiting SV40/luc expression, yet differed by just four amino acids. Mutation of D62 to alanine alone, or in combination with an E181 to alanine mutationmore »(D62A/E181A), dramatically reduced the ability of -IVb M to suppress host transcription. Introducing either M D62A or D62A/E181A mutations into VHSV-IVb via reverse genetics resulted in viruses that replicated efficiently but exhibited less cytotoxicity and reduced anti-transcriptional activities, implicating M as a primary regulator of cytopathicity and host transcriptional suppression. Importance: Viruses must suppress host antiviral responses to replicate and spread between hosts. In these studies, we identified the matrix protein of the deadly fish Novirhabdovirus, VHSV, as a critical mediator of host suppression during infection. Our studies indicated that M alone could block cellular gene expression at very low expression levels. We identified several subtle mutations in M that were less potent at suppressing host transcription. When these mutations were engineered back into recombinant viruses, the resulting viruses replicated well but elicited less toxicity in infected cells and activated host innate immune responses more robustly. These data demonstrated that VHSV M plays an important role in mediating both virus-induced cell toxicity and viral replication. Our data suggest that its roles in these two processes can be separated to design effective attenuated viruses for vaccine candidates.« less
4. Immuno-epidemiological co-affection model of HIV infection and opioid addiction

   https://doi.org/10.3934/mbe.2022168  

   Gupta, Churni ; Tuncer, Necibe ; Martcheva, Maia ( January 2022 , Mathematical Biosciences and Engineering)

   In this paper, we present a multi-scale co-affection model of HIV infection and opioid addiction. The population scale epidemiological model is linked to the within-host model which describes the HIV and opioid dynamics in a co-affected individual. CD4 cells and viral load data obtained from morphine addicted SIV-infected monkeys are used to validate the within-host model. AIDS diagnoses, HIV death and opioid mortality data are used to fit the between-host model. When the rates of viral clearance and morphine uptake are fixed, the within-host model is structurally identifiable. If in addition the morphine saturation and clearance rates are also fixed the model becomes practical identifiable. Analytical results of the multi-scale model suggest that in addition to the disease-addiction-free equilibrium, there is a unique HIV-only and opioid-only equilibrium. Each of the boundary equilibria is stable if the invasion number of the other epidemic is below one. Elasticity analysis suggests that the most sensitive number is the invasion number of opioid epidemic with respect to the parameter of enhancement of HIV infection of opioid-affected individual. We conclude that the most effective control strategy is to prevent opioid addicted individuals from getting HIV, and to treat the opioid addiction directly and independently frommore »HIV.

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5. Chloroviruses Lure Hosts through Long-Distance Chemical Signaling

   https://doi.org/10.1128/JVI.01688-18  

   Dunigan, David D. ; Al-Sammak, Maitham ; Al-Ameeli, Zeina ; Agarkova, Irina V. ; DeLong, John P. ; Van Etten, James L. ; Shisler, Joanna L. ( April 2019 , Journal of Virology)

   ABSTRACT Chloroviruses exist in aquatic systems around the planet and they infect certain eukaryotic green algae that are mutualistic endosymbionts in a variety of protists and metazoans. Natural chlorovirus populations are seasonally dynamic, but the precise temporal changes in these populations and the mechanisms that underlie them have heretofore been unclear. We recently reported the novel concept that predator/prey-mediated virus activation regulates chlorovirus population dynamics, and in the current study, we demonstrate virus-packaged chemotactic modulation of prey behavior. IMPORTANCE Viruses have not previously been reported to act as chemotactic/chemoattractive agents. Rather, viruses as extracellular entities are generally viewed as non-metabolically active spore-like agents that await further infection events upon collision with appropriate host cells. That a virus might actively contribute to its fate via chemotaxis and change the behavior of an organism independent of infection is unprecedented.