Lymphatic dissemination of simian immunodeficiency virus after penile inoculation

Zhong Min Ma, Joseph Dutra, Linda Fritts, Chris J Miller

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The human immunodeficiency virus (HIV) is primarily transmitted by heterosexual contact, and approximately equal numbers of men and women worldwide are infected with the virus. Understanding the biology of HIV acquisition and dissemination in men exposed to the virus by insertive penile intercourse is likely to help with the rational design of vaccines that can limit or prevent HIV transmission. To characterize the target cells and dissemination pathways involved in establishing systemic simian immunodeficiency virus (SIV) infection, we necropsied male rhesus macaques at 1, 3, 7, and 14 days after penile SIV inoculation and quantified the levels of unspliced SIV RNA and spliced SIV RNA in tissue lysates and the number of SIV RNA-positive cells in tissue sections. We found that penile (glans, foreskin, coronal sulcus) T cells and, to a lesser extent, macrophages and dendritic cells are primary targets of infection and that SIV rapidly reaches the regional lymph nodes. At 7 days after inoculation, SIV had disseminated to the blood, systemic lymph nodes, and mucosal lymphoid tissues. Further, at 7 days postinoculation (p.i.), spliced SIV RNA levels were the highest in the genital lymph nodes, indicating that this is the site where the infection is initially amplified. By 14 days p.i., spliced SIV RNA levels were high in all tissues, but they were the highest in the gastrointestinal tract, indicating that the primary site of virus replication had shifted from the genital lymph nodes to the gut. The stepwise pattern of virus replication and dissemination described here suggests that vaccine-elicited immune responses in the genital lymph nodes could help prevent infection after penile SIV challenge.

Original languageEnglish (US)
Pages (from-to)4093-4104
Number of pages12
JournalJournal of Virology
Volume90
Issue number8
DOIs
StatePublished - Apr 1 2016

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
vaccination
lymph nodes
Lymph Nodes
RNA
Human immunodeficiency virus
genitalia
HIV
Virus Replication
virus replication
infection
Vaccines
Infection
vaccines
Viruses
Foreskin
viruses
Heterosexuality
virus transmission

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Lymphatic dissemination of simian immunodeficiency virus after penile inoculation. / Ma, Zhong Min; Dutra, Joseph; Fritts, Linda; Miller, Chris J.

In: Journal of Virology, Vol. 90, No. 8, 01.04.2016, p. 4093-4104.

Research output: Contribution to journalArticle

Ma, Zhong Min ; Dutra, Joseph ; Fritts, Linda ; Miller, Chris J. / Lymphatic dissemination of simian immunodeficiency virus after penile inoculation. In: Journal of Virology. 2016 ; Vol. 90, No. 8. pp. 4093-4104.
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